10 - Pupillary Abnormalities

Question 1

History

Answer 1

1. Medications, ocular infections, face/neck trauma, headache, facial pain, diplopia, change in eyelid position
2. Examination: orbital exam, eyelid position, ocular motility

Question 2

Pupillary Examination

Answer 2

1. To evaluate pupils shine handheld light obliquely from below nose for indirect illumination and clear view of pupils in both darkness and room light https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3588138/
2. Avoid accomodative miosis by having patient fixate on distant target
3. Poor vision in 1 eye never a cause of anisocoria given consensual reflex
4. If light response abnormal, pupillary near response examined
   
   1. Lack of near response indicates patient not trying hard enough and may require auditory input in addition to visual stimulus like ticking watch
5. SLE essential

Question 3

RAPD

Answer 3

1. Optic nerve disorders: Unilateral optic neuropathies are common causes of RAPD.
   
   1. Demyelination Optic neuritis: Even very mild optic neuritis with a minimal loss of vision can lead to a very strong RAPD.
   2. Ischemic optic neuropathies: These include arteritic (Giant Cell Arteritis) and non-arteritic causes. Usually there will be a loss of vision or a horizontal cut in the visual field
2. Glaucoma: While glaucoma normally is a bilateral disease, if one optic nerve has particularly severe damage, an RAPD can be seen.
3. Traumatic optic neuropathy: This includes direct ocular trauma, orbital trauma, and even more remote head injuries which can damage the optic nerve as it passes through the optic canal into the cranial vault.
4. Post Surgical damage to the optic nerve: This could include damage following retrobulbar anesthesia; damage following orbital hemorrhage related to eye, orbital, sinus, or plastic surgery; damage following neurosurgical procedures such as pituitary tumor resection; and damage related to migration of an orbital plate after surgery to correct a blow-out fracture.
5. Hereditary optic neuropathies, such as Leber’s optic neuropathy (usually eventually bilateral) and other inheritable optic neuropathies.
6. Retinal detachment: A RAPD can often be seen if the macula is detached, or if at least two quadrants of retina are detached.
7. Ischemic retinal disease: Causes include ischemic central retinal vein occlusion, central retinal artery occlusion, severe ischemic branch retinal or arterial occlusions, severe ischemic diabetic or sickle-cell retinopathy.
8. Severe macular degeneration: If unilateral and severe, a RAPD can be seen. Usually the visual acuity would be less than 20/400.
9. Amblyopia: If severe, can lead to a relative afferent pupillary defect. Usually the visual acuity would be 20/400, or worse.

Question 4

Baseline Pupil Size

Answer 4

1. Baseline size dependent on ambient light, retinal adaptation, level of arousal, patient age.
2. Hippus — frequency and amplitude of both pupils oscillating rhythmically and in synchrony. Independent of variations in illumination or fixation
3. Ageing – decrease pupil size
4. Sleeping — inhibition of Edinger-Westphal nucleus causing small pupils
5. Elevated IOP — enlargement of pupils possibly due to iris ischemia
6. Seizures — dilated pupils
7. Extremely small pupils — pontine hemorrhage, narcotic intoxication, pilocarpine
8. Extremely large pupils — normal in young patients, parasympathetic blockade i.e. stimulants, high anxiety

Question 5

Pupil Irregularity

Answer 5

1. Congenital
   
   1. Coloboma
   2. Aniridia
2. Acquired
   
   1. Blunt trauma — focal tears in iris sphincter muscle
   2. Iridodialysis — outer edge of iris torn away from ciliary attachment
   3. Intraocular inflammation — Synechiae or ciliry spasm may cause small pupil
   4. Neovascularization
   5. Surgical pupil — cataract surgery. Large or small pupil.
3. Rare conditions:
   
   1. Tadpole pupil — focal spasm of iris dilator muscle usually associated with migraines. Small number of patients harbor underlying sympathetic lesion and Horner syndrome should be tested for
   2. Midbrain corectopia — eccentric or oval pupils in patients with rostral midbrain disease caused by incomplete damage of pupillary fibers leading to selective inhibition of iris sphincter tone.

Question 6

Anisocoria

Answer 6

1. First check pupillary light reflex to determine whether response to light normal
   
   1. If normal reaction to light (parasympathetic) then abnormality in sympathetic pathway
   2. If ONE pupil responds abnormally to light then examine iris sphincter at SLE

Question 7

Anisocoria EQUAL in dim and bright light

Answer 7

1. When magnitude of anisocoria equal in dim and bright light = physiologic anisocoria
2. Occurs in 20% of people
3. Difference in pupils less than 1.0mm and can vary from day-to-day
4. Sometimes more apparent in dim light than bright light and with ptosis on smaller pupil may create diagnostic confusion with Horner syndrome

Question 8

Anisocoria GREATER in DIM light

Answer 8

1. Mechanical or inflammatory origin
2. Obtain pharmaceutical history
3. Horner syndrome

Question 9

Horner Syndrome

Answer 9

1. Miosis (unopposed iris sphincter)
2. Facial anhidrosis
   
   1. Interruption of 1st order or 2nd order (preganglionic) neurons = anhidrosis of ipsilateral face, neck, head — one side of face is pale and other half is normal or reddish in color. Pale side = sympathetic deficit since blood vessels and perspiratory glands denervated!!!!
   2. Interruption of 3rd order nerve (post-ganglionic) result in anihidrosis to ipsilateral forehead.
3. Ipsilateral eyelid ptosis (Muller muscle denervation) & Mild lower eyelid elevation (reverse ptosis - denervation of lower tarsal muscle) — Narrow palpebral fissure and false impression of enophthalmos.
4. Congenital or long-standing Horner syndrome develop iris heterochromia — LIGHTER iris around 9-12 months of age
5. Difference between Horner and physiologic anisocoria since both may show anisocoria in dim light — pupillary dilation intact in physiologic anisocoria (sphincter relaxes and dilator contracts) vs Horner syndrome only sphincter can relax thus DILATION LAG (greatest at 4-5 seconds

Question 10

Horner Syndrome Cocaine

Answer 10

1. Cocaine blocks reuptake of NE = pupillary dilation
2. Horner syndrome — No NE released in synaptic cleft thus NO EFFECT seen
   
   1. Cocaine 4% or 10% and measure 45min - 1 hr later
3. Smaller pupil = side of Horner syndrome
4. Note: Eye with iris synechiae or immobile pupil can cause false positive results

Question 11

Horner Syndrome Apraclonidine

Answer 11

1. Alpha-2 agonist (sympatholytic) & WEAK alpha-1 agonist
2. Healthy eyes — little effect on pupil size (or constricts slightly)
3. Horner syndrome — Alpha-1 effect DOMINATES 2/2 supersensitivity of alpha-1 receptors resulting in dilation
4. Apraclonidine 0.5% or 1% each eye and assessed 1 hour later
   
   1. See REVERSAL of anisocoria
5. Apraclonidine limits:
   
   1. Only postganglionic neurons should produce denervation supersensitivity
   2. Denervation supersensitivity typically occurs 2-5 days after injury to sympathetic chain and acute injury questionable utility
   3. Avoided in young children — may cause CNS depression or acute respiratory distress. Cocaine better in kids
   4. Note: Brimonidine CANNOT be substituted as highly selective alpha-2 agonist and no effect on alpha-1 receptor on iris dilator

Question 12

Horner Syndrome Hydroxyamphetamine

Answer 12

1. Enhances release of presynaptic NE from postganglionic neuron. If pupil does NOT dilate after 1% hydroxyamphetamine = postganglionic neuron damaged (3rd order)
2. If both pupils dilate = 1st or 2nd order neuron damage
3. Cocaine may interfere with hydroxyamphetamine and should give 72 hours between tests

Question 13

Horner Syndrome Localization

Answer 13

1. 1st order
   
   1. Ataxia, nystagmus, hemisensory deficit suggests a medullary lesion indicating need for MRI Brain and upper cervical cord
2. 2nd order
   
   1. Arm pain, cough, hemoptysis, swelling in neck suggests mediastinum or superior sulcus pathology necessitating cervicothoracic imaging
3. 3rd order
   
   1. Numbness over V1 and V2 and diplopia from CN6 palsy that shares location of CN6 and oculosympathetic fibers in cavernous sinus
4. Carotid artery dissection = pain around temple and orbit and may extend to throat, amaurosis fugax and altered taste. Need emergent MRI
5. Trigeminal cephalgias = cluster headache may cause painful Horner syndrome during acute attack and if repeated attacks occur then may become permanent
6. Raeder paratrigeminal syndrome = Horner syndrome with daily unilateral headaches no characteristic of cluster headaches for which no underlying pathology found — diagnosis of exclusion, need imaging of brain, neck, spine, carotid arteries, chest, pulmonary apex with MRI/MRA/CT/CTA
7. Congenital = usually caused by birth trauma to brachial plexus. Non-traumatic Horner raises possibility of neuroblastoma from sympathetic chain of chest — MRI head, neck, chest and/or MRI abdomen warranted, UA to assess elevated levels of catecholamines

Question 14

Anisocoria GREATER in BRIGHT light - Iris damage

Answer 14

1. Iris damage
   
   1. Trauma = miosis or mydriasis. Pupil may be miotic immediately after injury due to spasm and therafter become mydriatic with poor response to light and near stimulation
   2. Will see TID and evidence of sphincter damage. Does NOT respond to pilocarpine 1% or 2% and mimics pharmoclogic mydriasis
   3. SLE = should identify traumatic mydriasis
   4. Iris injury in head trauma may be mistaken for CN3 palsy from uncal herniation
   5. Prolonged angle closure and intraocular surgery can impair pupillary function = Urrets-Zavalia syndrome

Question 15

Anisocoria GREATER in BRIGHT light - Pharmacologic

Answer 15

1. Pharmacologic mydriasis
   
   1. Anticholinergics accidentally or intentionally instilled in eye. Lose light and near stimulation
   2. Paralysis of entire sphincter muscle as opposed to sectoral palsy
   3. Pilocarpine 0.1% or 1% cannot reverse mydriasis
      
      1. Make the solution by diluting 1% pilocarpine with artificial tears to create a 1/10 (0.1%) concentration.
      2. With adrenergic mydriasis (phenylephrine) pupil is large + conjunctiva whitened + palpebral fissure enlarged + Accomodation not impaired vs anticholinergic mydriasis. Pilocarpine 1% causes some constriction in adrenergic mydriasis but more constriction without adrenergic mydriasis

Question 16

Anisocoria GREATER in BRIGHT light - Adie pupil

Answer 16

1. Adie tonic pupil
   
   1. 2/2 damage to ciliary ganglion or short ciliary nerves (postganglionic parasympathetic nerve)
   2. Large pupil with poor reaction to light but reaction to near vision aka light-near dissociation. Slow tonic redilation from near to far compared to normal eye — 30x more accomodative fibers than pupillary fibers thus damage to ciliary ganglion leads to robust remodeling and reinnervation in which accomodative fibers innervate pupillary sphincter abnormally. The misguided accomodative fibers sprout onto iris sphincter and pupil recovers ability to respond to accomodation HOWEVER pupillary movement delayed and slow (tonic). Light reflex remains impaired.
   3. Sectoral palsy of iris sphincter (stromal atrophy and thinning observed in areas of sphincter paralysis), accomodative paresis (acute and chronic but not subacute!) and denervation cholinergic supersensitivity
   4. Acute phase = pupil dilated and poorly reactive to light and accomodation
   5. Chronic phase = Months to years Adie pupil decreases in size (MIOTIC) but remains poorly reactive to light resulting in anisocoria greater in dim light than bright light as it stays miotic.
   6. Accomodative symptoms or photophobia usually respond spontaneously within few months — if photophobia problematic then piloicarpine 0.1% may be helpful
   7. Idiopathic Adie tonic pupil
      
      1. 70% females
      2. 80% unilateral and second pupil may become involved in 4%
   8. Holmes-Adie syndrome = includes diminished DTRs and orthostatic hypotension
   9. Etiology: Surgery, trauma, laser procedure, HSV, HZV, syphilis, botulism, inflammation, ischemia, DM, ETOH abuse, neurosyphilis, amyloidosis, sarcoidosis

Question 17

Adie Pupil Pilocarpine

Answer 17

1. Denervated iris sphincter muscle supersensitive to dilute pilocarpine 0.1%
   
   1. Affected pupil constricts more
   2. Develops within 5-7 days of denervation

Question 18

CN3 Palsy

Answer 18

1. If pupil involved need to rule out aneurysm
   
   1. Fixed and dilated pupil
2. If pupil spared then consider microvascular etiology
3. Constricts to 1% pilocarpine
4. Aberrant regeneration of CN3 may cause mydriasis and synkinetic pupillary reaction

Question 19

Light-Near Dissociation

Answer 19

1. Occurs when near response exceeds constriction from light
2. Near reflex (aka convergence reflex) bypasses pretectal nuclei in dorsal midbrain and descends from higher cortical centers directly to Edinger-Westphal nuclei — does NOT rely on photoreceptors to cause pupillary constriction

Question 20

Light-Near Dissociation

Answer 20

1. Etiology:
   
   1. Optic neuropathy damaging afferent limb of pupillary light reflex

Question 21

Light-Near Dissociation

Answer 21

1. Etiology
   
   1. Midrain lesions = Sparing of ventrally located fibers of near reflex and damage to Edinger-Westphal pathway. 2/2 infection, Argyll-Roobertson, syphilis, pinealoma, stroke, Parinaud syndrome
      
      1. Argyll Robertson — Seen in tertiary syphilis patients. Unlike Adie pupil, near response and subsequent dilation on far response is brisk. Also see TIDs, iris atrophy, poor dilation. Seen in diabetes, ETOH abuse, PRP (short ciliary nerves) and other autonomic neuropathies.
   2. Aberrant Regeneration = aberrant regeneration of damaged nerves that restore near reflex but not light reflex. 2/2 traumatic injury, chronic compression CN 3. Sometimes involves medial rectus muscle fibers and pupillary constriction occurs during adduction.

Question 22

Benign Epsiodic Unilateral Mydriasis

Answer 22

1. AKA springing pupil = young, healthy people with headaches. Episodic mydriasis accompanied by mild blurring, periocular discomfort and headache. Self-limited

Question 23

Paradoxical Pupils

Answer 23

1. Seen in inherited retinal disorders
2. Best Disease, Achromatopsia, RP, Albinism, Dominant Optic Atrophy, Optic Nerve Hypoplasia, Congenital Stationary Night Blindness, Leber’s Hereditary Optic Neuropathy