Neuro-ophthalmic Disorder
Disorders that affect the ocular muscles, ocular motor
(III, IV, and VI) cranial nerves, or visual or ocular
motor pathways in the brain produce a wide variety
of neuro-ophthalmic disturbances. Because the
anatomic pathways of the visual and ocular motor
systems traverse major portions of the brainstem and
cerebral hemispheres, neuro-ophthalmic symptoms
and signs are often valuable in the anatomic
localization and diagnosis of neurologic disease.
Anatomy of Visual System
Cranial Nerve
The extraocular muscles are innervated by the
oculomotor (III), trochlear (IV), and abducens (VI)
nerves. Because of this differential innervation of the
ocular muscles, the pattern of their involvement in
pathologic conditions can help to distinguish a
disorder of the ocular muscles from a disorder that
affects a cranial nerve. Cranial nerves that control eye
movement traverse long distances to pass from the
brainstem to the eye; they are thereby rendered
vulnerable to injury by a variety of pathologic
processes.
1. Oculomotor (III) nerve—The oculomotor nerve
supplies the medial rectus, superior and inferior
rectus, and inferior oblique muscles and carries fibers
to the levator palpebrae (which raises the eyelid). It
also supplies the parasympathetic fibers responsible
forpupillary constriction. With a complete nerve III
lesion, the eye is partially abducted, and cannot be
adducted elevated, and depressed; the eyelid droops
(ptosis), and the pupil is nonreactive.
2. Trochlear (IV) nerve—The trochlear nerve
innervates the superior oblique muscle. Lesions of
this nerve result in defective depression of the
adducted eye.
3. Abducens (VI) nerve—Lesions of the abducens
nerve cause lateral rectus palsy, with impaired
abduction of the affected eye.
Confrontation Test
Confrontation is the simplest method for visual field
testing. The examiner stands at about arm’s length
from the patient, with the eyes of both patient and
examiner aligned in the horizontal plane. The eye not
being tested is covered by the patient’s hand or an eye
patch. The examiner closes the eye opposite the
patient’s covered eye, and the patient is instructed to
fix on the examiner’s open eye. Now the monocular
fields of patient and examiner are superimposed,
which allows comparison of the patient’s field with
the examiner’s presumably normal field. The
examiner uses the index fingers of either hand to
locate the boundaries of the patient’s field, moving
them slowly inward from the periphery in all
directions until the patient detects them. The
boundaries are then defined more carefully by
determining the farthest peripheral sites at which the
patient can detect slight movements of the fingertips
or the white head of a pin. The patient’s blind spot can
be located in the region of the examiner’s own blind
spot, and the sizes of these spots can be compared
using a pin with a white head as the target. The
procedure is then repeated for the other eye.

Growth Hormone
GH is made in the somatotrophs throughout the
anterior pituitary.
Like other proteins it is synthesized as a larger
prehormone and GH exists in three molecular
forms.
GH appears to be a single copy gene but four
other hormones have significanthomology to
GH. For example prolactin has 16% homology
with GH and is made in lactotrophs  cannot
bind the GH receptor so it has no growth-
promoting activity. There are other peptides with
homology to GH and some can bind the GH
receptor.
Gh receptors are coupled to an intracellular
signalling system that involves stimulation of the
JAK family tyrosine kinases.
Somatotrophs secrete GH in a pulsatile fashion.
The pattern of bursts depends onsleep-wake
patterns. The increased output of GH results from
an increase in thefrequency rather than the
amplitude of the pulses.
Growth hormone secretion is under hierarchical
control from growth-hormone releasing
hormone and somatostatin. GH also releases
Somatomedine, an insulin-like growth factor
(IGF) that alters growth.
The hypothalamus secretes GH-releasing
hormone  promotes GH secretion. It is also
found in neuroectodermal tissue outside of the
CNS. GHRH binds to a G-protein coupled
receptor and activates G-alphas  increase in
cAMP  increased gene transcription and
synthesis of GH. It also increases
[Ca]  increased release of preformed GH.
Grehlin  distinct endocrine cells in
the mucosal layer of the stomach release
ghrelin in response to fasting (small amount
in hypothalamus)  increases GH secretion.
Binds to the GPCR designated GH secretagogue
receptor.
Secretion of GH is also regulated by feedback
loop involving IGF-1. GH triggers the secretion
of IGF -1  it has an endocrine effect on the
liver en more paracrine and autocrine effects on
muscle cartilage and bone. In increase in IGF-1
directly inhibits GH secretion from
somatotrophs. It also inhibits GH secretion by
suppressing GHRH and increasing SS.
Most of the GH circulates free in the blood but it
can be bound to GH-binding protein. The GH
receptor is a tyrosine kinase-associated receptor
and forms adimer when one GH molecule
simultaneously binds to sites on
two monomers  increases the activity
of tyrosine kinases  triggers actions in cells
that modulate target cell activity.
Effects of growth hormone
1. Short term  acute metabolic effects
include stimulation of lipolysis in
adipose tissue, inhibition of glucose
uptake by muscle and stimulation of
gluconeogenesis by hepatocytes.
2. Long term  mediated by IGF-1
Somatostatin is made in pancreas, GI
tract and hypothalamus. It inhibits
thesecretion of multiple hormones  GH,
gluvagon, gastrin, VIP and TSH.
Pituitary Gigantism Dwarfism
─ GH deficiency
─ GH excess caused by tumour cells of anterior
• treated by replacing GH
Pituitary Gigantism Growth Hormone tumour
cells of anterior pituitary producing GH • GH was extracted from human pituitary glands
─ in children this leads to gigantism at autopsy. Now made by recombinant tech
─ Hereditary
─ in adults acromegaly results (growth in stature
• Under-production of GHRH
does not occur because does not occur because
adult long bones are unable to lengthen • Incapable of manufacturing GH
─ Laron dwarf
Acromegaly • circulating GH levels ok but GH receptors
unable to bind
─ GH hypersecretion after adolescence causes
acromegaly
─ Certain benign tumors (adenomas) in pituitary
gland produces excess GH Acromegaly Growth
Hormone Progression of acromegaly
─ Features include
 Excessive thickening of bones
 Coarsened facial features
• Brow/lower jaw protrusion (enlarge jaw)
• Teeth spacing increase
 Soft tissue swelling of hands and feet
• Enlarged hands & feet Arthritis and carpal
tunnel syndrome D
• Arthritis and carpal tunnel syndrome
 Heart failure (major problem)
 Vision loss (compressed optic chiasm)
─ Medication reduce GH secretion/tumor
 Bromocriptine (DA receptor agonist)
 Somatostatin, to stop GH production
 GH receptor antagonists are emerging