Journal of Glaucoma
5:285-294, Lippincott-Raven Publishers, Philadelphia © 1996 Lippincott-Raven Publishers
Embryology, Anatomy, and Histology of the Optic
Nerve Vasculature
S. Orgiil, M.D., and G. A. Cioffi, M.D.
Devers Eye Institute/R. S. Dow Neurological Science Institute, Legacy Portland Hospitals, Portland, Oregon, U.S.A.
The details of the arterial supply to the optic nerve
command considerable interest because of the
presumed relevance to the pathophysiology of
glaucomatous optic neuropathy. Indeed, there is
abundant evidence suggesting that compromise of
the anterior optic nerve microvasculature plays a
role in the optic nerve damage seen in glaucoma (1).
As a consequence, the importance of examining the
ocular circulation in glaucoma has been emphasized.
The eye provides a unique opportunity to visualize
directly portions of the circulatory system in vivo.
The normal avascularity of certain ocular structures
such as the cornea, lens, and vitreous allows for
uninterrupted light transmission to the retina. The
retinal vasculature has been scrutinized
ophthalmoscopically for well over a century (2).
However, other parts of the ocular vasculature are
much more difficult to assess. The arterial supply to
the optic nerve has been extensively investigated,
but the precise anterior optic nerve microvascular
anatomy remains difficult to ascertain due to the
small vessel caliber, the complex three dimensional
architecture, and the relative inaccessibility of the
microvascular bed. A detailed knowledge of the an-
gio-architecture of the tissue examined, including
the optic nerve, must underpin an understanding of
the possible role of the vascular system in any
pathological process. The purpose of this review is
to briefly summarize the embryology, anatomy, and
histology of the anterior optic nerve
microvasculature. Because of the intricate nature of
the microvasculature in the posterior pole of the eye,
parts of the orbital, retinal, and choroidal vascula-
Received and accepted February 20, 1996.
Address correspondence and reprint requests to Dr. S. Orgiil,
Devers Eye Institute/Good Samaritan Hospital, 1040 NW 22nd
Ave., Ste. 200, Portland, OR 97210-3065, U.S.A.
ture will also be addressed. The arterial and venous
systems will be discussed together in the various
285
sections of the manuscript. Furthermore, it has been
shown that conclusions drawn even from findings in
subhuman primates are not always directly relevant
to humans (3). Therefore, anatomical description
pertaining to findings in nonhuman primates will be
properly annotated.
PRENATAL DEVELOPMENT OF THE
VASCULARIZATION OF THE
POSTERIOR SEGMENT
The development of the cerebral arteries received
little attention until the early post-WWII years (4).
Two principle time periods can be distinguished in
the prenatal development: the embryonic and the
fetal period. The embryonic period can be further
subdivided into “embryogenesis” and
“organogenesis,” and the fetal period involves the
differentiation of the primitive organs into fully or
partially active organs and is, therefore, sometimes
called “differentiation” (5). The current description
of the prenatal development of the eye will be
subdivided into the three following periods:
embryogenesis, organogenesis, and differentiation.
EMBRYOGENESIS
The first period of prenatal development,
embryogenesis, includes the establishment of the
primary organ rudiments. During this span of time,
the endothelial cells of the vessels originate in the
most medial region of the mesoderm, the paraxial
mesoderm (5). The pericytes of the blood vessels are
suspected to be of neural-crest origin (6). The period
of embryogenesis finishes at the end of gestational
week 3, when the optic groove appears on either
side of the midline at the expanded cranial end of
the still-open neural folds (7).
286 S. ORGUL AND G. A. CIOFFI
ORGANOGENESIS 6, the interior of the eye is drained by a terminal
Organogenesis is the second period of prenatal branch of the maxillary vein, which accompanies the
development. It starts at gestational week 4 and hyaloid artery (8). The capillary plexus surrounding
continues until the end of week 8. Week 4 is the optic cup drains into the superior and the inferior
characterized by the formation of the optic vesicle ophthalmic veins. The superior and the inferior
and by its invagination, transforming the optic ophthalmic veins, along with the maxillary vein
vesicle into the optic cup (8). The result of the connect to the cavernous sinus (Fig. 1).
invagination is the appearance of the embryonic The closure of the embryonic fissure is completed
fissure (9). This embryonic fissure allows a terminal during the first days of week 7 (11). This period is
portion of the dorsal opthalmic artery, a branch of characterized by a marked development of the
the prospective internal carotid artery, to penetrate periocular mesenchyme, culminating posteriorly in
into the developing optic cup (10). This branch will the formation of the choroidal vasculature. The
become the hyaloid artery with the beginning of primitive choriocapillaris is well formed and the
closure of the embryonic fissure. At this time, a channels of the capillaries are narrow. The
tributary of the primitive maxillary vein also lies endothelial cells facing the prospective Bruch’s
within the embryonic fissure and is thought to be the membrane have no fenestrations (13). Pericytes
precursor of the central retinal vein (11). Toward the appear on the endothelial cell walls adjacent to the
end of week 4, blood vessels cover the neural tube developing sclera.
and extend over the external surface of the optic The vascularization of the optic nerve begins in
cup. week 8 (14). The optic nerve is surrounded by
The development of the hyaloid vasculature and loosely packed meningeal cells. The meningeal cells
its anastomosis with the vessels outside the optic adjacent to the surface of the optic nerve
cup occurs during gestational week 5 (5). At this differentiate into pial cells (8,15). Capillaries
stage, invagination causes the obliteration of the develop along
cavity of the optic vesicle, as well as the progressive 6 weeks
occlusion of the lumen of the optic stalk (8). The
hyaloid artery communicates freely with the
SUPERIOR OPHTHALMIC VEIN
capillary plexus surrounding the optic cup through
the yet open embryonic fissure (12). Posteriorly, the
dorsal ophthalmic artery, which originates from the
prospective internal carotid artery and which
remains outside the optic cup, connects with the
capillary plexus covering the dorsal aspect of the
optic cup. The capillary plexus surrounding the optic
cup drain into the two main blood spaces, the
supraorbital and infraorbital venous plexuses, which
connect to the cavernous sinus (8).
The dominating factor in week 6 is the closure of
the embryonic fissure (5). The primitive choriocap-
illaris, which will be replaced later by the precursor
of the definitive choriocapillaris, begins to
differentiate with the development of the retinal
pigment epithelium during weeks 4 and 5 (13). In ARTERY
the periocular mesenchyme, the dorsal ophthalmic FIG. 1. By week 6, the capillary plexus surrounding the optic cup
drains into the superior and the inferior ophthalmic veins. These
artery branches along the temporal side of the optic vessels connect to the cavernous sinus. (Redrawn from ref. 65,
stalk and of the optic cup to form the common with permission.)
temporal ciliary artery, and the ventral ophthalmic with the differentiation of the pial cells. The
artery branches along the nasal side of the optic capillaries are either inside fibrous septa or
stalk and of optic cup to form the common nasal surrounded by a complete glial sheath. These
ciliary artery (10). These vessels are the precursors capillaries constitute the pial vascular plexus, which
of the temporal and nasal posterior ciliary arteries. starts to penetrate into the optic nerve within fibrous
The connection between the large vessels and the septa (16). A very large increase in vascularity of
microvasculature around the optic vesicle occurs the optic nerve occurs between weeks 8 and 18
later during the embryologic development. By week postconception, most of which occurs from week 12

J Glaucoma, Vol. 5, No. 4, 1996

 OPTIC NERVE VASCULATURE
onwards (16).
At the end of month 2, the primitive choriocapil-
laris is well-formed. Small arteries, two to three
layers thick, and venous blood vessels, composed of
a single layer of endothelial cells, can be identified perivascular spaces around the larger vessels, but
in the choroid (11). Rudimentary vortex veins
draining the primitive choriocapillaris appear as a
result of the confluence of the collecting channels.
At the same time, few short precursors of the
posterior ciliary arteries come out from the dorsal
ophthalmic artery, which will later become the main
ophthalmic artery after fusion with the ventral
ophthalmic artery (8) and connect with some larger
channels of the primitive choroidal vasculature.
DIFFERENTIATION
The third period in the prenatal development, the
differentiation, starts at the beginning of month 3
and involves the differentiation of each of the
primitive organs into a fully or partially active
organ. Toward the end of month 3, the pia mater is
more developed, and more blood vessels penetrate
into the optic nerve. These vessels are capillaries
separated from the axons by a complete astrocytic
sheath and a perivascular space (17). The primitive
choriocapillaris presents important changes. Some
capillaries enlarge and form a second layer of
choroidal vessels, while other capillaries disappear.
A new layer of capillaries, which will form the
definitive choriocapillaris, emerges beside the
retinal pigment epithelium (8). This transformation
into the definitive choriocapillaris begins at the
posterior pole and proceeds gradually toward the
anterior region (18). At the ultrastructural level, the which is the layer of medium-sized choroidal blood
endothelial cells of the definitive choriocapillaris
have numerous diaphragm-covered fenestrations on
the side facing the prospective Bruch’s membrane
and are attached to each other by tight junctions
(13). By the end of month 3 of gestation, the sclera
has surrounded the future choroid. Short posterior
ciliary arteries pierce the scleral condensation and
connect with the channels of the definitive
choriocapillaris, while two to three small branches
enter the primitive sclera to form the precursor of
the arterial circle of Haller and Zinn (8).
Month 4 is characterized by the maturation of the
retina and the appearance of the retinal
vascularization associated with the regression of the
hyaloid vascular system (5). The development of the
uveal vascularization, as well as the formation of the
arterial circle of Haller and Zinn, continues. In the
optic nerve, the amount of collagen increases in the
pial layers. Large bundles of collagen extend into
287
the optic nerve, carrying with them blood vessels,
and forming the septa. By this stage, the
vascularization of the optic nerve is well developed
(16). Cells similar to pericytes are found in the
not around the capillaries (19). New branches from
the short posterior ciliary arteries surround the
peripapillary zone and participate in the formation
of the arterial circle of Haller and Zinn (18). At the
posterior pole, the future Haller’s layer, which is the
layer of large-sized choroidal blood vessels, is
forming. These vessels drain into the vortex venous
system (8). With the increase in vascularization
during month 4, the lamina scleralis, which is
completely glial at the beginning of month 4,
becomes vascularized, and its vessels anastomose
with the capillaries of the optic nerve (17). The
vascularization of the lamina scleralis develops
when vascularized scleral connective tissue
penetrates into its glial septa. With the appearance
of connective-tissue septa in its structure, the lamina
scleralis becomes the lamina cribrosa.
Month 5 is characterized by the rapid growth of
the retinal vasculature (5). Spindle-shaped
mesenchymal cells deriving from the walls of the
hyaloid vessels form solid cords penetrating into the
nerve fiber layer of the retina. These cords canalize
into capillaries (20). When blood enters into these
capillaries, a venous outflow develops (21). Some
capillaries retract or atrophy, others enlarge and
become the main channels of the retinal blood
circulation. In the choroid, extensions from the short
posterior ciliary arteries and venules arising from
the choriocapillaris connect and form the
prospective middle choroidal layer, Sattler’s layer,
vessels (22). The vascularization of the meningeal
layers of the anterior optic nerve is complete.
During month 6, the retinal vasculature continues
to progress (5). At this stage, components of the
arterial circle of Haller and Zinn have anastomosed
(8,16), and the vascularization of the optic nerve is
complete.
The retinal vasculature continues to increase
during month 7, and, during month 8, the
development of the different tissues of the eye
markedly slows down (5).
During month 9, the retinal vessels reach the
temporal periphery, the retinal capillaries reach the
internal nuclear layer, and the hyaloid vessels
disappear (5).
At birth, the retinal vasculature is mature. The
lamina cribrosa is fully formed but still supple. It
becomes consolidated after birth (11).
J Glaucoma, Vol. 5, No. 4, 1996
 288 S. ORGUL AND G. A. CIOFFI
ANATOMY OF THE VASCULAR SUPPLY TO at the horizontal meridian of the globe, within the
THE POSTERIOR SEGMENT suprachoroidal space. The long posterior ciliary
arteries supply the iris, ciliary body, and the anterior
The vascular supply of the eye is composed of region of the choroid. After branching off the main
two separate systems: the retinal system and the posterior ciliary arteries, the short posterior ciliary
uveal system. The retinal system supplies the inner arteries course anteriorly and pierce the sclera
layers of the retina, and the uveal system supplies immediately adjacent to the optic nerve in the nasal
the choroid and the ciliary body. The choroid, in and temporal region. Occasionally, short posterior
turn, serves the outer retinal layers. The arterial ciliary arteries may have extrascleral anastomosis
supply of both systems is derived entirely from (28). The short posterior ciliary arteries supply the
branches of the ophthalmic artery. posterior choroid, as well as the majority of the
anterior optic nerve. The size and shape of the area
ORBITAL CIRCULATION of the choroid and optic nerve supplied by each
short posterior ciliary artery is variable among
The orbital contents are supplied by several
subjects and even between the eyes of a single
arteries, including the ophthalmic artery, the menin-
individual. Some short posterior ciliary arteries
golacrimal artery (a branch from the middle
course, without branching, through the sclera
meningeal artery), and palpebral arteries, which
directly into the choroid; others divide within the
branch from the facial artery (23). The middle
sclera to provide branches to both the choroid and
meningeal artery and the facial artery belong to the
the anterior optic nerve (29).
external carotid artery system. The ophthalmic
Often the medial and lateral paraoptic short
artery provides most of the blood supply to the eye
posterior ciliary arteries anastomose and form an
and is the first branch of the internal carotid artery,
elliptical circle around the optic nerve, —100-300
arising from the internal carotid artery after it turns
|xm posterior to the suprachoroidal space, the
to pierce the dura and emerges from the cavernous
arterial circle of Haller and Zinn (28-32). Branches
sinus (24). The vascular supply to the intraorbital
derived from the circle of Haller and Zinn include
optic nerve, retina, and choroid arises predominantly
recurrent pial branches, recurrent choroidal
from the ophthalmic arterial circulation via the
branches, and branches penetrating the optic nerve
posterior ciliary arteries, the central retinal artery,
(28). In subhuman primates, no arterial circle of
and the pial vascular network along the optic nerve
Haller and Zinn has been found (3,33-36). In the
(25). Except when it originates from the cavernous
human eye, this usually intrascleral, but occasionally
sinus, the ophthalmic artery exits the intracranial
extrascleral arterial network, has been suggested to
cavity through the optic canal and, in most
be incomplete in most instances (35,37,38). The
individuals, likes inferolateral to the optic nerve.
finding of an anatomically complete arterial circle of
The ophthalmic artery passes over the medial part of
Haller and Zinn would not necessarily imply that it
the optic nerve and turns medially in the orbit (26).
is functionally complete. Indeed, a recent
The ocular branches of the ophthalmic artery are the
investigation demonstrated in human intravascular
central retinal artery and one to five posterior ciliary
corrosion castings that the anastomoses between the
trunks, which usually divide into multiple branches,
lateral and medial short posterior ciliary arteries
forming separate groups of main posterior ciliary
form a complete elliptical circle around the optic
arteries (27).
nerve in 77% of the eyes, but that 43% of these eyes
Most individuals have two to three posterior
present narrow portions along the interarterial
ciliary trunks. When there are more than three, the
anastomoses (32).
additional vessels are usually small in size. The
The venous drainage of the orbit generally does
most common of these vessels are the medial and
not follow the arterial supply (39). The orbital veins,
lateral posterior ciliary trunks. These vessels can
in common with those of the head and neck, contain
sometimes be duplicated (30% and 20% of the
no valves. The largest of the orbital veins is the
individuals, respectively). In —9% of individuals, a
superior opthalmic vein, which accommodates the
superior posterior ciliary trunk can be found. Each
majority of the orbital venous effluent. The venous
main posterior ciliary artery divides further into
drainage of the retina and the anterior optic nerve is
several short posterior ciliary arteries, just before or
almost exclusively via the central retinal vein, which
after piercing the sclera. In addition, a medial and a
empties into the superior ophthalmic vein
lateral long posterior ciliary artery arise from the
(29,37,38). The choroid is drained through the
ciliary trunks, travel anteriorly, first along the
vortex venous system which empties into the
outside of the globe, and, after penetrating the sclera
superior and inferior ophthalmic veins. The superior

J Glaucoma, Vol. 5, No. 4, 1996

 OPTIC NERVE VASCULATURE 289
ophthalmic vein passes through the superior orbital anastomoses can enlarge to become
fissure, to empty into the cavernous sinus. It is often ophthalmoscopi- cally visible (45). The central
difficult to identify an inferior ophthalmic vein as retinal vein exits the eye through the optic nerve and
independent as the superior ophthalmic vein (40). parallels the central retinal artery. During its course
From a venous network, located anteromedially in through the optic nerve, the vein receives intraneural
the orbit, one branch arises which runs laterally and tributaries.
posteriorly under the optic nerve. This branch is the
inferior ophthalmic vein. It leaves the orbit through CHOROIDAL CIRCULATION
the inferior part of the superior orbital fissure.
Numerous anastomoses are generally present The choroid is by far the most vascular portion of
between the superior and inferior ophthalmic veins. the eye and one of the most vascular tissues in the
Both vessels drain into the cavernous sinus. body. The outer layer of the choroid, next to the
However, the inferior ophthalmic vein occasionally suprachoroidal space, contains the largest of the
drains into the pterygoid plexus through the inferior choroidal vessels (Haller’s layer). Anterior to
orbital fissure (41). Haller’s layer (toward to the outer retina), there is a
region of vessels of smaller caliber, known as Sat-
RETINAL CIRCULATION tler’s layer. The innermost layer, adjacent to Bruch’s
membrane is called the choriocapillaris and is
The retina derives its arterial supply from the composed of richly anastomotic, fenestrated
central retina artery and the underlying choroid. The capillaries beginning at the optic nerve margin (46).
central artery of the retina is usually the first branch The blood supply to the posterior choroid is
of the ophthalmic artery (27) and penetrates the provided by the short posterior ciliary arteries and
optic nerve —5-15 mm behind the globe (29,42). branch from the arterial circle of Haller and Zinn,
The central artery typically branches on the surface and the more anterior regions of the choroid are
of the disk and the adjacent peripapillary retina. supplied by the long posterior ciliary arteries and the
Occasionally, the central retinal artery may divide anterior ciliary arteries. Each short posterior ciliary
into superior and inferior trunks prior to reaching the artery or branch from the arterial circle of Haller and
anterior surface of the optic nerve. Typically, there Zinn provides blood supply to multiple choroidal
are four major trunks, one to each quadrant of the arterioles (47). Many choroidal arterioles can be
retina, which lie within the nerve fiber layer of the found in the outer choroid near the anterior optic
retina. This retinal circulation also supplies the most nerve, especially in the nasal and temporal region.
superficial layer of the optic nerve head (38). Anastomoses between the larger choroidal arteries
The superficial nerve fiber layer is supplied are not common, but they are frequent between the
principally by recurrent retinal arteries which smaller branches (48). From the smaller arteries, the
emerge in the peripapillary nerve fiber layer from terminal or precapillary arterioles that enter the
branches of the retinal arteries and which course chorio- capillaris arise. No contribution from the
toward the center of the optic nerve head (29). In chorio- capillaris to the capillaries of the anterior
>30% of normal eyes, a cilioretinal artery appears to optic nerve exists. Whether choroidal arteries supply
contribute to the retinal arterial supply (43). These the optic nerve has evoked controversy. Several
are vessels that supply a variably sized region of the studies suggested the presence of a choroidal arterial
retina, temporal to the optic nerve. Cilioretinal blood supply to the anterior optic nerve (49-51),
vessels emerge from the ciliary vascular system, whereas other investigators failed to demonstrate
either as a direct branch of the ciliary arteries or, in such a vascular supply (3,29,37,52).
rare instances, from the peripapillary choroid (44). Most of the vessels of the outer choroid, except
Cilioretinal arteries are end arteries, and the area of near the anterior optic nerve and the macula, are
retina supplied by such an artery receives no veins. Venous anastomoses are frequent in the
additional arterial input. choroid. Smaller veins merge to form large veins
The retinal venous drainage is via tributaries into which drain eventually into the vortical systems.
the major retinal veins which empty into the central Usually, four vortical systems are formed by the
retinal vein. The venous system extends as far confluence of choroidal veins, one in each of the
peripherally as does the arterial system. The central four quadrants, although this is very variable. The
retinal vein normally is the only outflow channel for vortex veins drain the choroid and the other parts of
the retinal circulation. Potential anastomoses exist the uveal coat (46) into the superior and inferior
between the retinal and choroidal circulation. In orbital veins.
cases of central retinal vein occlusion, these

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 290 S. ORGUL AND G. A. CIOFFI
BLOOD SUPPLY TO THE OPTIC NERVE
The arterial and venous vascularization of the
anterior optic nerve has been schematized in Figs. 2
and 3, respectively. The anterior portion of the op-
FIG. 2. The anterior optic nerve is supplied by the posterior
ciliary arteries and the central retinal artery. Immediately
posterior to the globe, the pial system is supplied by branches
of the central retinal artery (before it enters the optic nerve) and from the cilioretinal artery when it is present (50).
posterior ciliary arteries. LC, lamina cribrosa; NFL, superficial
nerve fiber layer; PL, prelamia; RL, retrolamina; CRA, central
retinal artery; C, choroid; PCA, posterior ciliary artery. (Modified region.
and reprinted from ref. 66, with permission.)
FIG. 3. The venous drainage of the anterior optic nerve is
almost exclusively via a single vein, the central retinal vein.
LC, lamina cribrosa; NFL, superficial nerve fiber layer; PL,
prelamia; RL, retrolamina; CRV, central retinal vein; C,
choroid; VV, vortex vein. (Modified and reprinted from ref. 66,
with permission.)
tic nerve may be divided into four regions: the
superficial nerve fiber layer, the prelaminar region,
the laminar area region, and the retrolaminar region
(38). The nerve fiber layer is not precisely defined
but can be delineated arbitrarily from the prelaminar
region by an imaginary plane extending across
Bruch’s membrane. It is composed primarily of the
axons extending from the retinal ganglion cells.
Immediately posterior to the nerve fiber layer is the
prelaminar region, which is adjacent to the
J Glaucoma, Vol. 5, No. 4, 1996
peripapillary choroid. It is distinguished by
hypercellular glial septae with minimal connective
tissue. More posteriorly, the laminar region is
continuous with the sclera and is a structure of
fenestrated, connective tissue lamellae, which allow
the transit of neural fibers through the scleral coat.
The retrolaminar region lies posterior to the lamina
cribrosa and is marked by meningeal sheaths,
myelinated axons, and delicate connective tissue
septae (37,53).
The superficial nerve fiber layer is supplied
principally from the arterioles in the adjacent retina
as suggested by filling of the superficial vessels
during the retinal arterial phase in fluorescein
angiography (54). Most of these vessels are
capillaries originating in the peripapillary nerve
fiber layer. These vessels, as with all capillary beds
within the optic nerve, are not fenestrated, and the
tight junctions between their endothelial cells
constitute the blood- ocular barrier. The temporal
nerve fiber layer may have an arterial contribution
No direct choroidal contribution is observed in this
The prelaminar region has fewer collagen septae
and more glia than does the laminar portion of the
optic nerve. This region receives arterial supply via
direct branches of the short posterior ciliary arteries
and via vessels originating from the arterial circle of
Haller and Zinn (29,35,55). As detailed above, the
posterior ciliary arterial system provides input to
both, the choroidal vessels and the arterial circle of
Haller and Zinn. The origin of the blood supply to
the prelaminar region of the anterior optic nerve has
evoked controversy. Extensive evaluations
suggested the presence of a choroidal arterial blood
supply to the prelaminar and laminar arterior optic
nerve (49,50). Indeed, fluorescein angiography
demonstrated the appearance of fluorescein in the
deeper regions of the anterior optic nerve
concomitantly with the filling of the choroidal
vessels. This suggests that this region of the nerve
receives the same arterial input as the choroid (51).
However, other investigators failed to demonstrate
such a vascular supply (3,29,37,52). The latter
authors argued, except for occasional small
arterioles, in favor of branches from the arterial
circle of Haller and Zinn and from the short
posterior ciliary arteries coursing through the
choroid, and, therefore, not really arising from it, but
merely passing through. The reason for the
discrepancy between the different studies remains to
be elucidated.
The lamina cribrosa portion of the optic nerve
contains numerous septae between bundles of axons.
 OPTIC NERVE VASCULATURE 291
The precapillary vessels perforate the outer aspect of exclusively via a single vein, the central retinal vein
the lamina cribrosa before branching into an (3,29,57). In the nerve fiber layer, blood is drained
intraseptal capillary network (55). The short by small veins that converge and empty, ultimately,
posterior ciliary arteries, either directly or via the into the central retinal vein. In the prelaminar,
arterial circle of Haller and Zinn, provide the laminar, and retrolaminar regions, venous drainage
principal arterial input to this portion of the optic also occurs via the central retinal vein or centripetal
nerve (3,37,55-57). The peripapillary choroid may tributaries to the central retinal vein. Occasionally,
contribute occasional small arterioles (29). small venules connecting the optic nerve and the
Most of the blood supply to the retrolaminar peripapillary choroid can be identified, mainly
portion of the optic nerve occurs through numerous within the prelaminar region (29). In the peripheral
perforating vessels from the pia mater (37). These aspects of the laminar and retrolaminar regions,
pial vessels obtain their supply either directly from some optic nerve venous drainage may also be via
the ophthalmic artery or indirectly from recurrent pial veins, but these pial veins ultimately drain into
branches back from the posterior ciliary arteries. the central retinal vein as it exits the optic nerve
The central retinal artery contributes by occasional (29).
(one to eight) small branches within the nerve to the
blood supply of the retrolaminar optic nerve, but not HISTOLOGY OF BLOOD VESSELS IN THE
for a significant amount (58). The central retinal OPTIC NERVE
artery may also inconsistently branch into the
retrobulbar optic nerve (23,25,50). However, a The anterior optic nerve is composed of the nerve
“central optic nerve artery” within the retrobulbar axons, the neuroglia, the blood vessels, and
optic nerve, as postulated in earlier investigations connective tissue. The neuroglial cells are astrocytes
(59,60) does not exist (58,61). Nevertheless, some and, in the retrobulbar optic nerve, also
authors have described “central optic nerve artery oligodendrocytes and microglia. An astrocytic
equivalents” (37), which are pial derived network surrounds the fascicles of nerve axons and
longitudinal arterioles in the retrolaminar nerve. is continuous from the retinal edge back through the
The rich capillary beds of the peripapillary retina, lamina cribrosa and the retrobulbar optic nerve (63).
the anterior optic nerve, and the retrolaminar region Astrocytes invest the connective tissue of all vessels
are anatomically confluent and form a continuous entering the anterior optic nerve. Unlike the retina,
vascular network along the anterior optic nerve where the processes of astrocytes often contact the
(3,29). These capillary interconnections unite the capillary wall, these processes are found only in
microvasculature along the length of the anterior close relation to the connective tissue around the
optic nerve. There is a subtle transition in the vessel wall in the prelaminar and the laminar regions
organization of the capillaries between the of the anterior optic nerve. Blood vessels in the optic
prelaminar and laminar regions. The capillaries of nerve, as elsewhere, can be identified on the basis of
the prelaminar region are complex and randomly wall-staining properties. Arteries are large, with
arranged, whereas the capillaries of the laminar multiple layers of smooth muscle cells, the
region conform to the pattern of the connective muscularis, surrounded by the adventitial layer. The
tissue septae which compose the laminar supportive latter consists of circumferentially oriented collagen
architecture. The capillaries become fewer behind fibrils which blend with fibers in the perivascular
the lamina (62). The presence of this longitudinal space. An inner elastic lamina separates the
anastomosis of capillaries might be viewed as a muscularis from the endothelium. A basement
protective mechanism against regional ischemic membrane surrounds the endothelial cells and
insult, but the functional importance of these blends with the internal lamina elastica. The internal
potential collaterals is not known. Flow resistance lamina elastica is made of elastic fibers. As the
may be so high in these fine capillaries that it limits arteries diminish in caliber, they become arterioles.
potential collateral flow. Indeed, the presence of Arterioles are distinguished by their singular layer
potential collateral arterial supplies may have little of smooth muscle cells, no, or only minimal,
functional significance in the acute occlusion internal elastic lamina, and relatively dense reticulin
setting, because the ischemic neuronal damage may lining. The adventitia is continuous with collagen
transpire before regional alterations in blood flow fibers in the intravascular space. The endothelium is
occur. continuous and the cells are covered by a basement
Remarkably, in view of the abundant arterial membrane. Precapillaries and capillaries can be
supply from many source vessels, the venous identified by their minimal wall thickness, their
drainage of the anterior optic nerve is almost basement membrane staining (positive periodic

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 292 S. ORGUL AND G. A. CIOFFI
acid-Schiff reaction), and the mural cells (pericytes). nerve differs from those in the laminar and
Larger capillaries have some reticulin fibrils in the retrolaminar portions by a lack of an internal elastic
outer part of the basement membrane which mark lamina and a complete absence of elastic tissue in
the transition zone between capillary and arteriole or the media (63). The vascular pattern of the
capillary and venule. The endothelium, basement superficial nerve fiber layer is one of a network of
membranes and mural cells of venules are vessels from the prelaminar region and branches
indistinguishable from those of the capillaries. from the central retinal artery and main retinal
Collagen appears in the outer wall, and a thickening arteries (37). Vessels derived from the vascular bed
of the basement membrane can be seen as the of the retinal arteries tend to be arterioles and
venules enlarge. The wall of the veins consists of a precapillaries, whereas those from the prelaminar
continuous inner lining of endothelial cells, a media region tend to be precapillaries and capillaries.
with elastic fibers and a few irregularly and When cilioretinal arteries are present, precapillary
intermittently spaced smooth muscle cells, and a branches to the superficial nerve fiber layer can be
thin, spare adventitia of fibrocytes and collagen seen. The venous drainage within the anterior optic
fibers. Within the anterior optic nerve, all the nerve occurs via centripetal tributaries to the central
arterial, capillary, and venous channels resemble, retinal vein. The structure of the venules changes
ultrastructurally, those of the central nervous very little in different portions of the anterior optic
system. They are nonfenestrated and have tight nerve (63).
junctions. They do not leak fluorescein or other As the capillaries enlarge, reticulin and collagen
tracers. Therefore, this mi- crovascular bed forms a appears in their outer wall which marks their
blood-nerve barrier. transition to venules. While the venules enlarge, a
Large arterioles are uncommon within the optic thickening of the basement membrane occurs and an
nerve. Vessels with continuous muscle layers are interrupted layer of muscle cells develops. Small
almost never seen. In fact, it is rare to see anything veins drain into the central retinal vein. The latter’s
other than capillaries within the anterior optic nerve wall consists, within the anterior optic nerve, of an
(64). The intraseptal vessels of the retrolaminar endothelium, a muscularis, consisting of elastic
optic nerve are primarily large precapillaries and fibers and two to three layers of smooth muscle
capillaries, derived from arteries and arterioles cells, and a thin adventitia (63).
emanating from the pial sheath (37). The pial
arterioles become capillaries as they pass through CONCLUSION
the pial septae into the axial portion of the nerve.
The lamina cribrosa is supplied by transversely The vascular anatomy of the anterior optic nerve
entering vessels. The vessels entering the posterior has been extensively studied. However,
portion of the lamina cribrosa are larger (arterioles) controversies regarding the exact vascular supply to
than those entering the anterior portion the various regions within the anterior optic nerve
(precapillaries, and capillaries) (37). Capillaries are still exist. Furthermore, as with any biological
observed regularly in the laminar portion of the system, the physiological implications that can be
nerve. They have a continuous unfenestrated derived based solely on studies of anatomy are
endothelium and most often course through the limited. Nevertheless, a detailed knowledge of the
connective tissue septae. Capillaries entering the complex angioar- chitecture of the anterior optic
nerve fascicles have a very thin layer of adventitial nerve must underpin an understanding of the
connective tissue, which is surrounded by possible role of the vascular system in glaucomatous
astrocytes. Occasionally, pericytes or their processes optic neuropathy.
are seen along the outer endothelial surface of some Acknowledgment: This research was supported in part
capillaries (63). The outer surface of the pericytes by the Schweizerische Stiftung fur medizinisch-
also shows a basement membrane. The biologische Stipendien and by National Institutes of
angioarchitecture in the prelaminar region is Health grant EY05231.
characterized by a diffuse network of arterioles,
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