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PUPIL/OPTIC NERVE VARIOUS PATHWAYS AND ABNORMALITIES DR. PRADEEP BASTOLA Associate Professor, Department of Ophthalmology (NGMCTH) 5/10/2015 Improving health worldwide www.lshtm.ac.uk

References :

References Walsh & Hoyt's Clinical Neuro-Ophthalmology, 6th Edition Adlers physiology of the eye 7 th edition A.A.O. 2010-2011 section 5 Ophthalmology 2 nd volume: Myron and Yanoff Oxford text book of Ophthalmology Clinical ophthalmology By Jack J. kanski (Newer edition) A text book of Ophthalmology (Goldberg, Paymen) Various sources from Internet (Emedicine and articles)

Important Terminologies:

Important Terminologies Optic chiasma (Decussating point of Optic nerves) Optic tract (Formed by ipsilateral Temporal fibre and contralateral nasal fibre) Lateral geniculate body (Optic radiations or to pretectal nucleus) Pretectal nucleus: Get way to parasympathetic supply to Pupil Edinger Westphal nucleus Ciliary ganglion (Post ganglionic fibres to sphincter pupillae, IIIrd Nerve) Short ciliary nerves Anisocoira (Significant difference in pupil size in same person, 0.4mm – 1mm) Corectopia: Abnormally placed pupil Polycoria: More than one aperture in the Iris of an eye Ectropion Pupillae: Everted puillary margin

Presentation layout :

Presentation layout Introduction/Anatomy Parasympathetic control of Pupillary size Light stimulus Parasympathetic control of Pupillary size Near point stimulus Sympathetic control of Pupillary size Abnormal Pupillary reactions Clinical Implications

Pupil-introduction :

Pupil-introduction Aperture in the centre of iris Circularly arranged constrictor muscles Parasympathetic (Oculomotor Nerve) Radially arranged dilator muscles Sympathetic (Short ciliary nerves) (Pupillary unrest and hippus)

Normal Pupil:

Normal Pupil Round, Regular: 3 - 4 mm in size (2- 5 mm reported) Myopic eyes: Larger pupil (Room condition) Hypermetropic eyes: Smaller pupil (Room condition) Smaller in infants : dilator muscle not well developed Large in Adolescent : sympathetic over action Small in old age : Fibrotic sphincter Premature baby has no pupillary light reaction until 31 weeks of gestation Small during sleep Sympathetic activity reduced Parasympathetic activity enhanced

Pupillary Reflex Pathway:

Pupillary Reflex Pathway

Parasympathetic Control of Pupillary Size:

Light Stimulus Optic Nerve Optic Tract Pretectal Nucleus (Synapse) Ciliary ganglion Short Ciliary Nerves Sphincter Pupillae Constriction of Pupil. Parasympathetic Control of Pupillary Size Optic Chiasm (Nasal fibres cross to opposite side) III Cranial Nerve of Both Sides Edinger Westphal Nucleus of both sides

Where does the impulse begin?:

Where does the impulse begin? Begins in the retina with the photoreceptors No separate receptors for visual and pupillary fibers

Contd…. :

Contd…. Ganglion cells First order neuron Melanopsin containing ganglion cells – major contributor in the midbrain serving the classic pupillary light reflex pathway .

Melanopsin containing ganglion cells..???:

Melanopsin containing ganglion cells..??? P hotosensitive , with a broad spectral peak centering on about 490 nm P roject to the suprachiasmatic nucleus in the hypothalamus and to the pretectal nucleus P rovide light sensing information to the hypothalamus -modulate the circadian rhythm

Inter neurons of light reflex:

Inter neurons of light reflex Optic nerve Optic chiasma Nasal fibres crosses so that one optic tract serving for homonymous field Optic tract Pretectal nucleus Edinger-Westphal nuclei Bilateral and equal innervations Ganglion cell fibers destined for the pretectal region of the mesencephalon leave the optic tracts before reaching the LGN

The efferent arc of the pupillary light reflex:

The efferent arc of the pupillary light reflex Visceral oculomotor nuclei 1.Edinger-Westphal nuclei neurons serving for pupillary light reflex 2. Anterior median nuclei primary neurons involved in accommodation 3. Nucleus of Perlia Pic from camera

Pupillary Fibers in the Oculomotor Nerve:

Pupillary Fibers in the Oculomotor Nerve Saggital reconstruction of brain stem with course of third nerve Emergence from brain stem Mid point in sub arachnoid space Where third nerve enters the dura At anterior cavernous sinus where third nerve divides

Ciliary Ganglion and Short Ciliary Nerves:

Ciliary Ganglion and Short Ciliary Nerves Site of the synapse with the preganglionic parasympathetic fibers 2 mm X 1 mm 1 cm anterior to the medial end of the superior orbital fissure 1 . E W nucleus 2. 3 rd nerve 3. Branch to inferior oblique 4. Ciliary ganglion 5. Short ciliary nerves

Contd…. :

Contd…. Parasympathetic ganglia About 3-5% supply the iris sphincter (Sphincter pupillae ) About 95-97% ciliary muscle

Ciliary Ganglion and Short Ciliary Nerves contd…:

Ciliary Ganglion and Short Ciliary Nerves contd… 8 to 20 short ciliary nerves leave ciliary ganglion in two or three bundles Postganglionic, parasympathetic fibers ( synapse over there) Postganglionic, sympathetic vasomotor Afferent sensory fibers of the trigeminal nerve

Parasympathetic Control of pupillary Size Near Point Stimulus – Controversial Pathway::

Retina Optic Nerve Optic Chiasma Optic Tract Lateral Geniculate body Optic Radiation Occipital Cortex Frontal Lobe (undetermined pathway) Edinger Westphal Nucleus (undetermined pathway) Ciliary Ganglion III Nerve Short ciliary nerve Sphincter Pupillae Parasympathetic Control of pupillary Size Near Point Stimulus – Controversial Pathway :

Near Reflex:

Near Reflex Two components: Convergence Reflex Accommodation Reflex Triad of Synkinetic Near Response: Convergence Accommodation of lens Constriction of pupil

Near Reflex:

Near Reflex Pathway for near reflex is more ventrally located than that for light reflex Anatomical basis for some instances of light-near dissociation of the pupils

Sympathetic Outflow Pathway:

Sympathetic Outflow Pathway Final common path of active dilator impulses extends from the hypothalamus to the iris. Long three-neuron arc Hypothalamus to the lateral cervical cord Spinal cord to superior cervical ganglion Superior cervical ganglion to the orbit and iris


Contd… Uncrossed and lateral position in the brain stem Ciliospinal center of Budge and Waller in anterolateral columns Synapse with the preganglionic neurons at C8 to T2. Preganglionic Sympathetic Fibers proceed close to the pleura at the apex of the lung

Slide 23:

7. s c g 8 i c a 9, e c a 10, sudomotor fibers to face; 11, carotid plexus; 12, caroticotympanic nerve; 13, tympanic plexus; 14, deep petrosal nerve; 15, lesser superficial petrosal nerve; 16, sympathetic contribution to vidian nerve; 17, ophthalmic division of the trigeminal nerve; 18, nasociliary nerve; 19, long ciliary nerve; 20, ciliary muscle and iris dilator muscle; 21, probable pathway of sympathetic contribution to retractor muscles of the eyelids; 22, vasomotor and some sudomotor fibers; 23, o a 24, lacrimal gland; 25, short ciliary nerves; 26, salivary glands; 27, greater superficial petrosal nerve

Sympathetic Control of Pupillary Size:

Posterior Hypothalamus Brain Stem Cranial Spinal Cord Synapse at C 8 T 1-2 Superior cervical ganglion synapse Along internal carotid artery Cavernous sinus 6 th Nerve (briefly) 5 th C.N. (Ophthalmic) Nasociliary branch Ciliary ganglion (No synapse) Long ciliary nerve Dilator pupillae Sympathetic Control of Pupillary Size

Supranuclear influences :

Supranuclear influences Excitatory influence in the visceral nuclei of the oculomotor complex Arrives via centrifugal pathways from the occipital cortex 2. Pupil constriction to near stimuli 3. Distributed ventrolaterally in the upper midbrain 4. Mainly to the anterior median nucleus : near reflex Light near dissociation in isolated lesion of pretectal region

Other pupillary reflexes:

Other pupillary reflexes Darkness reflex abolition of light reflex, contraction of dilator pupillae Psycho sensory reflex cortical reflex loud noise or pain causes pupillary dilatation Lid closure reflex constriction of pupil with blinking

Inhibitory Influences:

Inhibitory Influences Dark Reaction Light-adapted eye is suddenly exposed to darkness, pupils dilate Dilation still occurs even after the sympathetic innervation is interrupted Cortical and Hypothalamic Inhibition parasympathetic outflow inhibited by corticothalamo-hypothalamic corticolimbic pathways Fatigue and drowsiness loss of inhibition pupil constrict Sleep pupils are small but react to light Miosis is a release phenomenon

Inhibitory Influences contd…:

Inhibitory Influences contd… Brain Stem and Spinal Cord Inhibition Ascending spinoreticular pathways produce direct inhibition Mydriasis occurs with arousal or painful stimuli is reduced but not eliminated by sympathectomy even in a decerebrate, sympathectomized preparation

Abnormal Pupillary Reactions:

Abnormal Pupillary Reactions Afferent pupillary conduction defects Efferent pupillary defects Pupillary light near dissociation Anisocoira D/D: Essential anisocoria  Adie pupil (long-standing) Argyll-Robertson pupil Chronic anterior uveitis Pupillary sphincter tear Unilateral use of miotics or mydriatics Third nerve palsy Ptosis : Aponeurotic ptosis Ocular myasthenia Third nerve palsy  (ptotic eye has the larger pupil) Congenital ptosis

Afferent Pupillary Conduction Defects:

Afferent Pupillary Conduction Defects Total Afferent Pupillary Defect ( TAPD) Amaurotic Pupil Complete optic nerve lesion Relative Afferent Pupillary Defect (RAPD) Incomplete optic nerve lesion Severe retinal disease Extensive Amblyopia Wernicke’s Hemianopic Pupil Midline optic chiasma lesion Optic tract lesions

Normal Vs RAPD:

Normal Vs RAPD

Slide 33:

RAPD is an objective sign of unilateral or asymmetric disease of the optic nerve head or retina mostly. Grading Scale:  RAPD Grade 0: No reaction Grade 1+:   A weak initial pupillary constriction followed by greater redilation Grade 2+:   An initial pupillary stall followed by greater redilation Grade 3+:   An immediate pupillary dilation Grade 4+:   No reaction to light – Amaurotic pupil

Causes of RAPD:

Causes of RAPD Optic Nerve Disorders Unilateral or asymmetric bilateral optic neuropathy Retinal Disease Presence of a RAPD usually indicates macular involvement Amblyopia A small RAPD Media Opacities Dense vitreous hemorrhage


Contd….. Optic Tract Disorders a small to moderate RAPD in the contralateral eye Pretectal Nucleus lesion A unilateral lesion in the pretectal nucleus Contralateral RAPD without any visual field defect

Efferent Pupillary Defects:

Efferent Pupillary Defects Absence of direct and consensual light reflex on the affected side Presence of direct and consensual light reflex on the normal side

Slide 38:

On the affected side, near reflex is absent Pupil -dilated and fixed Alarming to an physician because third-nerve palsy must be ruled out

Slide 39:

Causes of fixed dilated pupils Mid brain damage CVA Tumors Degenerative conditions Damage to third nerve Pharmacological eg; Atropine Trauma: Damage to the sphincter pupillae

Light near dissociation of pupil:

Light near dissociation of pupil Better pupillary response to near than to light Causes Lesions of retina eg RD Optic, nerve tract, optic tract Midbrain lesion in pretectal Argyll Robertson pupil


Anisocoria Difference in the size of two pupils is more than 0.4 mm 20% of the general population below18 years prevalence rises to 33% persons over 60 years

Contd.. :

Contd.. Physiologic anisocoria Most common cause of anisocoria 41% have anisocoria of 0.4mm or more when observed for 5 days 19% have anisocoria at any given time 20% have less than 1mm difference Anisocoria equal in dim and bright light Consistent with physiologic anisocoria


Contd…. Anisocoria greater in dim light Posterior synchiae Pharmacologic anisocoria-miotics Physiologic anisocoria Dilate normally after cocaine installation without dilatation lag Horner syndrome

Horner syndrome (Anisocoria, anophthalmos, anhydrosis):

Horner syndrome (Anisocoria, anophthalmos, anhydrosis ) Any lesion in the oculosympathetic pathway results in Horner syndrome

Contd…. :

Contd…. Ipsilateral ptosis,miosis and anhydrosis Other features anisocoria, dilatation lag herterochromia iridis increased accommodation in the affected side

Causes :

Causes First-order neuron lesions Arnold-Chiari malformation Cerebral vascular accident Demyelinating disease Intrapontine hemorrhage Pituitary tumor Syringomyelia

Contd…. :

Contd…. 2 nd -order neuron lesions Pancoast tumor Birth trauma with injury to lower brachial plexus Cervical rib Aneurysm/dissection of aorta Neuroblastoma Trauma/surgical injury 3 rd -order neuron lesions Internal carotid artery dissection Carotid cavernous fistula Cluster/migraine headaches Herpes zoster

Slide 48:

Few tests to confirm Horner's syndrome & in identifying the level of damage Dilation lag Cocaine test: 2 drops of 10% cocaine – dilates the normal pupil 1% Hydroxyamphetamine test: Differentiation between pre – ganglionic & post - ganglionic Horner's syndrome anisocoria increases in post-ganglionic type

Anisocoria :

Anisocoria Anisocoria greater in bright light Iris damage(sphincter damage) Pharmalogic dilatation Adies tonic pupil Third nerve palsy

Adies Tonic Pupil :

Adies Tonic P upil Sluggish segmental pupillary response to light Better response to near effort followed by slow redilatation Caused by post ganglionic parasympathetic damage

Adies tonic pupil contd…… :

Adies tonic pupil contd…… Supersensitive to parasympathomimetics Due to denervation hypersupersensitivity Histopathologically-reduction in the number of ganglion cells in the ciliary ganglion

Third Nerve Palsy :

Third Nerve P alsy Pupillary involvement is almost always accompanied by ptosis and limitation of extraocular mobility Maximum anisocoria occurs in bright light Aneurysms at the junction of internal carotid and posterior communicating artery must be excluded If pupil is spared aneurysm is unlikely Causes Basal aneurysm Supratentrorial SOL Basal meningitis Ischaemic oculomotor palsy (DM), Vasculitis

Argyll Robertson Pupil (ARP) :

Argyll Robertson Pupil (ARP) Occurs in neurosyphilis Affected pupil are small(less than 2 mm), regular Do not react to light but near reaction is normal Even miotic pupil reacts briskly to near stimuli Mnemonic: ARP: Accommodation Reflex Present PRA: Pupillary reflex absent

Hutchinson’s pupil :

Hutchinson’s pupil Comatosed patient with unilateral dilated poorly reacting pupil (Young adult/Elderly giving history of heavy alcohol intake and fall in the bathroom or toilet in the morning ====== tell tell history) Suggestive of ipsilateral expanding intracranial supratentrorial mass (hematoma) “Neurosurgical Emergency if not diagnosed in time patient can die due to large subdural hematoma”

Pourfour Du Petit Syndrome (Opposite Horner Syndrome):

Pourfour Du Petit Syndrome (Opposite Horner Syndrome) Rare dysautonomic complication due to brachial plexus block Mydriasis, eyelid retraction, and hyperhydrosis. PDPs was first described by Francois Pourfour Du Petit (1664-1741), a French physician. Signs of increased sympathetic Activity in the eyes and upper extremity following slashed wound of neck with sword.  

Flow chart to evaluate anisocoria:

Flow chart to evaluate anisocoria

Summary of tests:

Summary of tests

Visual Field Deficits after Lesions at Various Levels of the Visual System:

Visual Field Deficits after Lesions at Various Levels of the Visual System Optic nerve: transection = monocular blindness. Optic chiasm: ( e.g ., pituitary tumour). Transection  bitemporal visual field deficit. Optic tract or LGN: transection  contralateral visual field deficits (homonymous hemianopsis). Optic radiations: transection of Meyer’s Loop only (temporal region)  contralateral upper quadrant (‘quadranotopia’). Complete transection  homonymous hemianopsia. 1° Visual Cortex: most common = infarction  homonymous hemianopsia with macular sparing ( 2° greater cortical representation).

Visual field lesions and defects:

Visual field lesions and defects

Optic Nerve:

Optic Nerve 2 nd cranial nerve Sensory Starts from optic disc, extends to optic chiasma where two nerves meet. It is backwards continuation of retinal nerve fibers which consists of the axons originating from the ganglion cells. It is not a peripheral nerve, but rather a white matter tract of central nervous system. There are two optic nerves, each connecting the retina within each globe to the target areas within the brain.


STRUCTURE OF NERVE 1.2 million myelinated fibers 53% crosses in optic chiasma Not a nerve in true sense- direct extension of brain Lacks neurilemma so unable to regenerate. Potential sub-arachnoid & subdural spaces. Macular fibers lie medially- assumes central position at optic foramen.


PARTS OF OPTIC NERVE Total length:- 47-50 mm Intra-ocular part:- 1 mm Intra-orbital part:- 30 mm Intra- canalicular part :- 6-9 mm Intra-cranial part:- 10 mm


INTRA OCULAR PART Intraocular part passes through sclera (converting it into a sieve-like structure—the lamina cribrosa), choroid and finally appears inside the eye as optic disc. Lamina cribrosa : The nerve fibres forming the  optic nerve  exit the eye Posteriorly through a hole in the  sclera  that is occupied by a mesh-like structure called the  lamina cribrosa . It is formed by a multilayered network of collagen fibres that insert into the sclera canal wall. The nerve fibers that comprise the optic nerve run through pores formed by these collagen beams.


INTRAORBITAL PART Extends from back of eyeball to optic foramina. It is 30mm in length . The straight line distance from back of the globe to optic canal is much less , with relative excess of the optic nerve being necessary for free movement of globe during eye movement. Here it travels within the cone formed by 4 recti muscles near the optic foramina . So tumour with in the cone are common source of compression of optic nerve or compressive optic neuropathy. In addition, enlargement of the muscles themselves particularly inferior. rectus, med rectus. eg in grave’s Ophthalmopathy may compress the nerve.


Contd.. Posteriorly, near the optic foramina, it is closely surrounded by the annulus of Zinn and origin of 4 recti muscles. Some fibres of the superior rectus muscle are adherent to its sheath here , and accounts for the painful ocular movements seen in retrobulbar neuritis. Anteriorly, the nerve is separated from the ocular muscles by the orbital fat.

Intaorbital part of optic nerve:

Intaorbital part of optic nerve


INTRAORBITAL PART CONT…….. Crossed superiorly by- Ophthalmic artery from lateral to medial side. Superior ophthalmic vein Nasocilliary nerve medial to lateral side. Crossed inferiorly by- Nerve to medial rectus At the apex- cilliary ganglion lie between optic nerve & lateral rectus. Near eye ball-there is retro ocular fat.


INTRACANALICULAR PART 6 to 9 mm in length. C losely related to ophthalmic artery- inferolaterally, covered in dura. Sphenoid & posterior ethmoid sinus lie medially and separated by thin bony lamina which accounts for retrobulbar neuritis following sinus infection . Within the canal and immediately post to canal , meningeal tissue is adjacent to optic nerve so benign tumour of meninges or meningioma are common causes of compressive optic neuropathies in these location.


INTRACANALICULAR PART Closely related to ophthalmic artery- inferolaterally. Sphenoid & posterior ethmoid sinus lie medially Retrobulbar Optic neuritis following sinus infection.


INTRACRANIAL PART This part lies above cavernous sinus converge with the fellow nerve over diaphragma sellae to form optic chiasma . There is highly variable length of nerve until optic chiasma is reached i.e. 8 to 9 mm




OPTIC CHIASMA Chiasma means crossroad. Here nasal fibres crosses and temporal at temporal are destined to remain ipsilateral . The %age of the fibres that cross versus that do not is anatomically 53:47. Optic chiasma is flat & Quadrangular in shape 12mm (horizontally) and 8mm ( antero-posteriorly) Rest of tuberculum sellae & diaphragm sella. The latter is app. 10 mm between the inferior part of the nerve and sup. Part of the pituitary so tumors of the pituitary which enlarges enough to compress chiasma may cause compressive optic neuropathy. The chiasma is prefixed in(ant displaced) in app. 10 %, post fixed in 75% of subjects.

Although the optic nerve anatomically ends at the optic chiasma, the retinal ganglion axons continue within the optic tract until lateral geniculate nucleus, superior colliculus, pretectal nuclei or hypothalamus.:

Although the optic nerve anatomically ends at the optic chiasma, the retinal ganglion axons continue within the optic tract until lateral geniculate nucleus , superior colliculus , pretectal nuclei or hypothalamus.

Visual Pathway:

Visual Pathway


OPTIC TRACTS These are cylindrical bundles of nerve fibres running outwards and backwards from the postero-lateral aspect of the optic chiasma. Each optic tract consists of fibres from the temporal half of the retina of the same eye and the nasal half of the opposite eye. Posteriorly each optic tract ends in the lateral geniculate body. The pupillary reflex fibres pass onto pretectal nucleus in the midbrain through the superior brachium. S ome fibres terminate in the superior colliculus.


LATERAL GENICULATE BODIES These are oval structures situated at the posterior termination of the optic tracts. Each geniculate body consists of six layers of neurons (grey matter) alternating with white matter (formed by optic fibres). The fibres of second-order neurons coming via optic tracts relay in these neurons.

Lateral geniculate nucleus:

Lateral geniculate nucleus

Slide 82:

OPTIC RADIATION The fresh fibres from the lateral g eniculate body form the geniculo-calcarine tract(optic radiations) which ends in the visual area of the cerebral cortex, These consist of the axons of third order . VISUAL CORTEX It is located on the medial aspect of the occipital lobe , above and below the calcarine fissure. It is subdivided in to the visual-sensory area (striate area 17) that receives the fibres of the radiations, and the surrounding visual- psychic area (peristriate area 18 & parastriate area 19)


BLOOD SUPPLY OF OPTIC NERVE The visual pathway is mainly supplied by pial network of vessels except the orbital part of optic nerve which is also supplied by an axial system derived from the central artery of retina. The pial plexus around different parts of the visual pathway gets contribution from different arteries. Visual pathway is supplied by- Pial plexus Calcarian artery Posterior cerebral artery Anterior choridal artery

Blood supply of visual pathway by pial plexus:

Blood supply of visual pathway by pial plexus

Slide 85:

Blood supply of the optic nerve head The surface layer of the optic disc is supplied by capillaries derived from the retinal arterioles. The prelaminar region is mainly supplied by centripetal branches of the peripapillary choroid with some contribution from the vessels of lamina cribrosa. The lamina cribrosa is supplied by branches from the posterior ciliary arteries and arterial circle of Zinn. The retrolaminar part of the optic nerve is supplied by centrifugal branches from central retinal artery and centripetal branches from pial plexus formed by branches from the choroidal arteries, circle of Zinn, central retinal artery and ophthalmic artery.

Lesions of the visual pathway 1. Optic nerve 2.Proximal part of optic nerve; 3. Central chiasma 4. Lateral chiasma (both sides) 5. Optic tract 6.Geniculate body 7. Part of optic radiations in temporal lobe 8. Part of optic radiations in parietal lobe 9. Optic radiations 10. Visual cortex sparing the macula 11. Visual cortex, only macula:

Lesions of the visual pathway 1 . Optic nerve 2.Proximal part of optic nerve; 3. Central chiasma 4. Lateral chiasma (both sides ) 5. Optic tract 6.Geniculate body 7. Part of optic radiations in temporal lobe 8. Part of optic radiations in parietal lobe 9. Optic radiations 10. Visual cortex sparing the macula 11. Visual cortex, only macula

Next class 1. Optic Nerve 2. Visual pathway 3. Visual field defects 4. Optic atrophy causes:

Next class 1. Optic Nerve 2. Visual pathway 3. Visual field defects 4. Optic atrophy causes

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