EMBRYOLOGY, ANATOMY, AND PHYSIOLOGY OF THE AFFERENT VISUAL PATHWAY

35

B
Figure 1.37. Wilbrands knee in human tissue. A, Woelcke myelin stain of a horizontal section through the optic chiasm
from a patient whose left eye was enucleated 5 months before death. There is reduced myelin staining in the left optic nerve
(arrow), but there is no evidence of Wilbrands knee. B, Woelcke myelin stain of a horizontal section through the optic chiasm
from a patient whose right eye was enucleated 2 years before death. There is more pronounced atrophy of the right optic nerve,
and a small Wilbrands knee is evident (arrow). (Courtesy of Dr. Jonathan Horton.)

nerve corresponds generally to their distribution in the retina.

The outflow from the papillomacular bundle is positioned
temporally within the anterior optic nerve (Fig. 1.35), then
gradually moves centrally in the more posterior optic nerve
(303305). Intracranially, the axons partially lose their retinotopy because of the decussation of some axons (306). The
macular projection does not have a precise localization in
the posterior nerve (307).
Historically, a Wilbrands knee was believed to exist at
the junction of the optic nerve and chiasm, where a small
number of inferonasal retinal axons were believed to cross
into the opposite optic nerve and pass anteriorly for a few

millimeters, then turn back posteriorly to enter the chiasm

(308,309). The knee is now believed to be an artifact
(310). A knee can be created by removal of one eye (310).
Apparently, the gliotic reaction secondary to optic nerve atrophy over a period of years distorts the anterior chiasm,
pulling some axons into an aberrant location (Figs 1.36 and
1.37). Thus, a knee is not present normally. A paradox
therefore exists, given that visual field defects produced by
compressive lesions at the anterior chiasm often include a
contralateral, superotemporal field depression (i.e., junctional scotoma), which heretofore was explained by the presence of a knee.

OPTIC CHIASM
EMBRYOLOGY
The optic chiasm is a commissure formed by converging
optic nerves anteriorly and diverging optic tracts posteriorly
(Fig. 1.38). During development, the chiasmal anlage separates from the floor of the third ventricle, maintaining contact
only at the boundary between its posterior aspect and the
anterior-inferior wall of the third ventricle (Fig. 1.39).
The location of the chiasm is established by the first RGC
fibers that arrive, which occurs between the fourth and sixth
week of development. The next fundamental step is the
proper routing of the incoming axons. Numerous factors
contribute to the directional preferences of the arriving axons
(311,312) (Fig. 1.40). Glia within the optic nerve and some
highly conserved molecules are believed to be instrumental
to the process (306,313318). For instance, Zic2 is expressed early in retinal development in the cells that will
project ipsilaterally, and thus Zic2 may endow these cells
with response properties that influence their trajectory at the

chiasm. The differential spatial and temporal expression of

the Pax2 gene by the growing axons and the sonic Hh gene
at the developing chiasm are also likely relevant to the formation of the decussation (319). Specialized glial cells in
the developing diencephalon extend their radial processes,
which physically interact with the incoming axons (306).
These glial cells express Eph/ephrinA molecules, which influence the growth of axons within the chiasm (see also the
section on the retina). Metalloproteases, which modulate the
interaction of local environmental cues with growth cones
extending from the distal axons, also seem to be relevant
for proper wiring (320). Axons that remain uncrossed tend
to reach the chiasm before those that will cross, which might
expose the different populations to time-varying changes in
the local environment (321,322).
The decision point is apparently not binary for these incoming axons. Real-time video microscopy has revealed that
axons move through the chiasm in a pulsed, saltatory fash-

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CLINICAL NEURO-OPHTHALMOLOGY

Figure 1.38. The optic chiasm viewed from

below. Note relationships of the mammillary bodies, oculomotor nerves (III nerve), and cerebral
peduncles to the chiasm. (Redrawn from Pernkopf
E. In: Ferner HA, ed. Atlas of Topographical and
Applied Human Anatomy. Vol 1. Philadelphia,
WB Saunders, 1963.)

ion. All axons that approach the chiasmal midline display

especially long pauses in activity, with ameboid movements
of their growth cones, which assume a more complex morphology than is typical of advancing axons (323,324). Following this complex orchestration near the end of 3 months
of gestation, an adult-like hemidecussation is established.
The shape of the developing optic chiasm differs from
that of the mature chiasm. The evolution in shape partly
relates to the shift from a lateral to eventually a frontal position of the eyes in the head. In the second half of gestation the
gross anatomic changes include (a) progressive narrowing of
the angle between the two optic nerves to about 45 degrees,
without a corresponding change in the angle formed by the
optic tracts; (b) separation of the chiasm from the diaphragma sellae and pituitary gland with development of the
chiasmatic cistern; (c) progressive elevation of the chiasm
above the optic foramina; and (d) thinning of attachments
of the chiasm to the floor of the third ventricle.
Rarely, a chiasm does not form, and this can occur despite
normal development of the fovea (325,326). Malformation

of the fovea and chiasm occurs in patients with albinism.

Deficient melanin production leads to an abnormally small
uncrossed projection, perhaps because of the timing of RGC
development (discussed previously) rather than to some influence at the chiasm per se (312). In particular, albino mice
have fewer Zic2-positive retinal neurons than their pigmented counterparts, which (given the putative role of Zic2
described above) may explain the diminished ipsilateral projection (327). The disordered chiasmal projection in albinos
can be recognized by MRI, which can reveal a smaller chiasmal width and a relatively wide angle between the optic
nerves and the optic tracts (328).
GROSS ANATOMY OF THE CHIASM AND
PERICHIASMAL REGION
The optic chiasm has a transverse diameter of 1020 mm,
an anteroposterior width of 413 mm, and thickness of 35
mm (262,329). The optic chiasm is covered, except where
attached to the brain, by arachnoid and pia mater, the latter

EMBRYOLOGY, ANATOMY, AND PHYSIOLOGY OF THE AFFERENT VISUAL PATHWAY

37

Figure 1.39. Midsagittal section through the cerebral hemispheres, showing the position of the optic chiasm relative to the
third ventricle and basal cisterns. (Redrawn from Pernkopf E. In: Ferner HA, ed. Atlas of Topographical and Applied Human
Anatomy. Vol 1. Philadelphia, WB Saunders, 1963.)

being continuous with the pia of the optic nerves and part
of the optic tracts. The optic chiasm is in direct contact with
CSF anteriorly within the subarachnoid space, and posteriorly within the third ventricle (Fig. 1.39 and 1.41), features
easily visualized with MRI (Fig. 1.42).
Inferiorly, the optic chiasm lies over the body of the sphenoid bone, typically above the diaphragma sellae and (paradoxically) only rarely within the sulcus chiasmatis (330)
(Fig. 1.25). The relative position of the chiasm over the sella
turcica is variable. The chiasm is (a) above the tuberculum
sellae (i.e., prefixed) in 12%; (b) above the diaphragma
sellae in 79%; and (c) above the dorsum sellae (i.e., postfixed) in 4% of cases (264,330) (Fig. 1.41). In patients
with brachycephaly, the chiasm typically is more rostral and
dorsal than in dolichocephaly. This variability of position
partially accounts for the variable patterns of visual field
defects seen in patients with upwardly expanding pituitary
adenomas.
The intracranial optic nerves do not lie on a horizontal
plane; rather, they rise upward from the optic canals at an

angle of 1545 degrees (331). The chiasm lies above the

diaphragma sellae, the dural covering of the sella turcica, by
approximately 10 mm (332335) (Fig. 1.43). The sphenoid
sinuses lie under the chiasm only when they extend far back
into the body of the sphenoid bone. In one third of adults,
an arachnoid membrane extends outward from the infundibulum to fuse with arachnoid around the carotid arteries and
the inferior surface of the chiasm (336).
The shape of the pituitary gland varies considerably
among individuals. The width of the gland is typically
greater than or equal to its depth or length. The lateral and
superior margins of the gland are more variable in shape
because they are not confined within bone. Rarely, the pituitary gland protrudes inferiorly into the sphenoid sinus (264).
Superiorly, the lamina terminalis, which defines the anterior end of the diencephalon, extends upward from the chiasm to the anterior commissure. The A2 segments of the
anterior cerebral arteries pass medially and upward above
the optic chiasm. The anterior cerebral and anterior communicating arteries may be situated above the chiasm or the

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CLINICAL NEURO-OPHTHALMOLOGY

Figure 1.40. Trajectory of retinal ganglion cell axons during early and late phase of chiasm formation. Horizontal view of
axon growth and cells of the ventral diencephalon during the early (E12E13) and later (E15E16) phases of axon growth.
Specialized radial glia (small dots) form palisades on either side of the midline and express RC2 as well as Slit2 (rostrally),
EphA and EphB receptors, and NrCAM. The early-born neurons (large dots) express CD44 and SSEA-1 as well as ephrinAs,
Slit 1, Robo1 and Robo2, and disulfated proteoglycans. Slit1 is expressed dorsal to and around the optic nerve as it enters the
brain and more weakly by the CD44/SSEA neurons. Slit2 is strongly expressed in the preoptic region directly dorsal and
anterior to the chiasm. A, At E15E16, during the major phase of retinal axon divergence, growth cones have different forms
depending on their locale and behavior. Crossing (thick line) and uncrossed (thin line) fibers have slender streamlined growth
cones in the optic nerve and optic tract. Near the midline, all axons pause and have more spread forms. Uncrossed growth
cones extend along the midline in highly complex shapes before turning back to the ipsilateral optic tract. B, In the early phase
of retinal axon growth, the first-born uncrossed retinal axons from the dorsocentral retina (DC) enter the ipsilateral optic tract
directly, quite far from the midline. In contrast, in the later period, uncrossed axons travel toward the midline and diverge from
crossing axons within the radial glial palisade. Crossed axons at both ages traverse the midline close to the rostral tip of the
early-born neurons. All retinal axons at both ages grow around the contours of the early-born neurons. C, Maneuvers of retina
axons with respect to the resident cells of the optic chiasm. DC, dorsocentral; D, dorsal; V, ventral; N, nasal; T, temporal.
(From Mason C, Erskine L. The development of retinal decussations. In: Chalupa LM, Werner JS, eds. The Visual Neurosciences.
Cambridge, MA, MIT Press, 200497.)

optic nerves, or they may rest directly on these structures

(Fig. 1.44). The junction of the anterior communicating artery with the A1 segments usually occurs above the chiasm
rather than the optic nerves (263). Laterally, the ICAs
emerge from the cavernous sinuses and approach the posterior optic nerves and sides of the chiasm. Occasionally, the
ICAs contact and compress these structures. Posteriorly, the
chiasm is bounded by the third ventricle, which explains

the vulnerability of the chiasm to compression or infiltration

by lesions within the ventricle or even an expanded ventricle.
ORGANIZATION OF NERVE FIBERS WITHIN THE
OPTIC CHIASM
Several generalizations can be made about the topography
of fibers passing through the chiasm, although much of our
knowledge in this regard derives from nonhuman primates.

Figure 1.41. Three sagittal sections of the optic chiasm and sellar region showing the positions of a prefixed chiasm above
the tuberculum sellae (left), a normal chiasm above the diaphragma sellae (center), and a postfixed chiasm above the dorsum
sellae (right). The W-shaped clear zone behind the chiasm is the anterior aspect of the third ventricle. (Redrawn from Rhoton
AL Jr, Harris FS, Renn WH. Microsurgical anatomy of the sellar region and cavernous sinus. In: Glaser JS, ed. NeuroOphthalmology Symposium of the University of Miami and the Bascom Palmer Eye Institute. St Louis, CV Mosby,
197775105.)

Figure 1.42. MRIs of the normal optic chiasm. A, Noncontrast T1-weighted image shows position of the optic chiasm in sagittal
section. Note the angle made by the incline of the intracranial portion of the optic nerve as it approaches the chiasm (arrowhead).
B, T1-weighted image after contrast administration shows the position of the body of the chiasm in coronal section.

Figure 1.43. Relationships of the optic nerves and

optic chiasm to the sellar structures and 3rd ventricle
(III); C, anterior clinoid; and D, dorsum sellae. (Redrawn
from Glaser JS. Neuro-ophthalmology. Hagerstown,
MD, Harper & Row, 1978.)

39

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CLINICAL NEURO-OPHTHALMOLOGY

Figure 1.44. Anterior views of the A1 and proximal A2 segments of the anterior cerebral arteries,
anterior communicating arteries, and recurrent arteries, showing variations in their relationship to
the intracranial optic nerves and optic chiasm. Gyri
recti and olfactory nerves are located superiorly.
(From Perlmutter D, Rhoton AL Jr. Microsurgical anterior cerebralanterior communicating
recurrent artery complex. J Neurosurg 1976;
45259272.)

First, the proportion of crossed fibers is always greater than

the uncrossed population, typically with a ratio of roughly
5347 in humans (293). Second, retinal fibers projecting to
the ipsilateral dLGN come only from the temporal retina,
whereas fibers projecting to the contralateral dLGN come
only from the nasal retina. The separation between crossed
and uncrossed fibers begins just as the fibers reach the chiasm. Uncrossed fibers, both dorsal and ventral, maintain
their relative position through the lateral chiasm and pass
directly into the ipsilateral optic tract (310). Crossed fibers

from the dorsal retina project more caudally in the chiasm

than crossed fibers of the ventral retina. An exception to
these principles occurs for fibers that project to the superior
colliculi, which project from throughout the retinae (337).
Third, macular projections are both crossed and uncrossed
and constitute a large percentage of the chiasmal fibers. Macular fibers are more concentrated dorsally and centrally and
are generally not present in the inferior rostral and caudal
regions of the chiasm (68,307,329,338). Fourth, retinohypothalamic axons exit the chiasm posteriorly (without entering

EMBRYOLOGY, ANATOMY, AND PHYSIOLOGY OF THE AFFERENT VISUAL PATHWAY

the tracts) to reach the hypothalamus. Finally, some retinal

fibers, especially those of melanopsin-containing RGCs (discussed previously), bifurcate and project to two central sites
after they emerge from the chiasm.
BLOOD SUPPLY
The distal optic nerves, optic chiasm, and proximal optic
tracts pass below the anterior communicating artery and anterior cerebral arteries and above the posterior communicating arteries, PCAs, and basilar artery (339) (Figs. 1.33 and
1.44). The chiasm obtains blood from branches of all of these
surrounding vessels. There is considerable interindividual
variation in the blood supply of the chiasm (329). In general,

41

the chiasmal blood supply comes from a dorsal and ventral

group of feeder vessels. The dorsal supply derives from
branches of the ICA, usually via superior hypophyseal arteries, the A1 and occasionally the A2 segments of the anterior
cerebral artery, and the anterior communicating artery.
Branches from more distal stretches of the anterior cerebral
artery typically supply some of the dorsal chiasm (265,340).
The ventral supply derives from branches of the posterior
communicating artery, PCA, and basilar artery (339). The
superior hypophyseal artery, a branch of the ICA, often provides blood to the ventral chiasm (284). There is often significant collateralization among these vessels (341), which explains the utter rarity of chiasmal infarction.

OPTIC TRACT
The optic tract, which is fully formed by the 13th week
of gestation, is the segment of the afferent visual pathway
between the chiasm and dLGN. From their origin, the optic
tracts diverge in front of the interpeduncular space and wind
laterally above the uncus and then around the internal cap-

sule to reach the dLGN (Figs. 1.38, 1.45, and 1.46). Unlike
the intracranial optic nerves, the optic tracts are firmly attached to the brain throughout their course by glial cells.
Each tract contains crossed and uncrossed fibers, most of
which synapse in the dLGN. A few tract fibers turn medially

Figure 1.45. The optic tracts and lateral geniculate body viewed in sagittal section. Note the relationship of the optic tract
to the internal capsule and corticospinal tract. The pulvinar is just medial to the lateral geniculate body. (Redrawn from Pernkopf
E. Atlas of Topographical and Applied Human Anatomy. Vol 1. Philadelphia, WB Saunders, 1963.)