Physiology and abnormalities of the pupil

The pupil is an opening in the center of the iris through which light enters the eye. Pupillary size can vary in response to light intensity and neurologic stimuli. Increasing brightness causes pupillary constriction (miosis) while increasing darkness causes pupillary dilation (mydriasis). Pupillary abnormalities can be caused by a variety of conditions.

• Isocoria: the pupils of both eyes are the same size
  • Normal pupil diameter: ^[1]
    • In bright light: 2–4 mm
    • In the dark: 4–8 mm
• Fixed pupil: the absence of pupillary response to a light stimulus or convergence testing
• Afferent neural pathway (afferent limb)
  • Registration of light stimulus in the eye and transmission of the impulse to the central nervous system
  • Isolated unilateral afferent pupillary defect (e.g. optic neuritis) → pupils are isocoric
    • Illumination of the affected eye leads to reduced/absent constriction of both pupils.
    • Illumination of the unaffected eye leads to normal pupillary constriction in both eyes.
• Efferent neural pathway (efferent limb): impulse transmission to the iris sphincter muscle
  • Parasympathetic nervous system mediates motor innervation of the iris sphincter muscle
  • Sympathetic nervous system mediates motor innervation of the iris dilatator muscle
  • Isolated unilateral efferent pupillary defect (i.e. impairment of the pupillary reflex) → pupils are anisocoric

• Accommodation: adjustment of the eyes to different distances (near vision versus far vision)
  • Primarily mediated by the lens, which changes convexity to adapt the refractory power.
  • Changes occur via contraction of ciliary muscles and are mediated by the Edinger-Westphal nuclei bilaterally.
    • Relaxed ciliary muscle → tense ciliary processes → curvature of lens decreases
    • Constricted ciliary muscle → relaxed ciliary processes → curvature of lens increases
• Convergence
  • Simultaneous inward movement of both eyes to maintain focus on close objects (e.g., eyes crossing when looking at one's own nose)
  • Occurs via the medial recti muscles bilaterally and is mediated by the oculomotor nerve (CN III).
• Accommodation reflex: The synkinetic constriction of the pupil (miosis), convergence of the eyes, and accommodation of lens convexity in response to a suddenly closer object.
  • Miosis: contraction of iris sphincter muscle
  • Convergence: contraction of both medial rectus muscles → eyes look inward
  • Accommodation: preganglionic parasympathetic fibers from Edinger-Westphal nucleus travel with the oculomotor nerve → ciliary muscle contraction → increased lens convexity

Pupillary control ^[2]

Pupillary control is mediated by both parasympathetic and sympathetic innervation.

Mydriasis

• Definition: dilation of the pupil (> 4 mm in daylight)
• Mechanism
  • Contraction of the iris dilator muscle (surrounds the peripheral part of iris)
    • Innervated by sympathetic fibers
      • First-order neuron: sympathetic hypothalamic fibers → lateral intermediate columns of the spinal cord → ciliospinal center of Budge (C8–T2)
      • Second-order neuron: preganglionic sympathetic fibers (exit from the T1 segment of the spinal cord) → rises to the upper cervical region along the cervical sympathetic trunk (passes near subclavian vessels and lung apex) → sympathetic trunk → superior cervical ganglion
      • Third-order neuron: postganglionic sympathetic fibers form a plexus along the internal carotid artery → cavernous sinus → plexus forms long ciliary nerve and enter superior orbital fissure → dilator muscle of the iris (pupillary dilation), superior tarsal muscle of the eyelid (upper eyelid retraction), sweat glands of the upper face
  • Indirectly by relaxation of the iris sphincter muscle

Miosis

• Definition: constriction of the pupil (< 2 mm in daylight)
• Mechanism
  • Contraction of the iris sphincter muscle (surrounds pupil)
    • Innervated by parasympathetic fibers
      • First-order neuron: fibers from Edinger-Westphal nucleus → oculomotor nerve fibers (located in the periphery of the oculomotor nerve) → ciliary ganglion
      • Second-order neuron: ciliary ganglion → short ciliary nerves → pupillary sphincter
  • Indirectly by relaxation of the iris dilator muscle

Short ciliary nerves make the pupillary muscle fibers short (leading to miosis), while long ciliary nerves make the pupillary muscle fibers long.

Pupillary light reflex

• Definition: constriction of the pupils in response to light
• Types
  • Direct pupillary reflex: constriction of the pupil in response to ipsilateral light stimulation
  • Indirect pupillary reflex (consensual pupillary reflex): constriction of the pupil in response to illumination of the contralateral eye
• Anatomical pathway of nerve fibers
  1. Retinal ganglion cell neurons (first-order)
     • Impulses from the retina travel in the afferent optic nerve (CN II) to the optic chiasm
     • At the optic chiasm
       • Fibers from the temporal half of the retina → ipsilateral optic tract → ipsilateral pretectal nucleus in the midbrain
       • Fibers from the nasal half of the retina crossover → contralateral optic tract → contralateral pretectal nucleus
  2. Internuncial neurons (second-order): Fibers from each pretectal nucleus innervate both the ipsilateral and contralateral Edinger-Westphal nuclei.
  3. Preganglionic parasympathetic motor neurons (third-order): efferent limb arises from Edinger-Westphal nucleus → oculomotor nerve (CN III) → ciliary ganglion
  4. Postganglionic parasympathetic motor neurons (fourth-order): arise from the ciliary ganglion → short ciliary nerves → iris sphincter muscle → direct and consensual pupillary constriction

• Description: impaired pupillary constriction due to a defect in the afferent pathway of the pupillary light reflex
• Etiology
  • Optic nerve lesions (e.g., optic neuritis, retrobulbar neuritis in multiple sclerosis, anterior ischemic optic neuropathy, glaucoma)
  • Severe retinal disease (e.g., central retinal artery occlusion, extensive retinal detachment)
  • Maculopathy (macular degeneration)
  • Optic tract lesions (e.g., infarction)
• Clinical features
  • Unilateral afferent pupillary defect (relative afferent pupillary defect, Marcus Gunn pupil)
    • Indicates a unilateral or asymmetric defect of the afferent pathway of the pupillary light reflex
    • Positive swinging flashlight test
      • Light stimulus shone onto a normal eye results in intact direct pupillary reflex and indirect pupillary reflex (i.e., constriction of both pupils).
      • Light stimulus rapidly transferred to the affected eye results in impaired direct pupillary reflex and indirect pupillary reflex (i.e., dilation of both pupils).
  • Bilateral: impaired direct and indirect pupillary reflexes in both eyes

• Definition: a difference in size between pupils > 1 mm
• Etiology
  • Physiological anisocoria: idiopathic
    • Occurs in up to 20% of individuals ^[3]
    • Size difference between pupils is typically < 1 mm
    • Degree of anisocoria does not change in response to changes in ambient light
    • Typically intermittent and self-limiting but can be persistent in some individuals
  • Nonphysiological anisocoria: size difference between pupils is typically > 1 mm
    • Disorders of the iris
      • Anterior uveitis
      • Acute angle closure glaucoma
      • Eye trauma or eye surgery
      • Congenital defects (e.g., iris coloboma, heterochromia iridis)
    • Disorders affecting sympathetic or parasympathetic innervation of the pupil
      • If a sympathetic defect or parasympathetic overactivity → pupillary constriction
      • If a parasympathetic defect or sympathetic overactivity → pupillary dilation
      • May be pharmacological or nonpharmacological

• Diagnostics: light reflex
  • If the light reflex is poor in one eye, perform a slit lamp examination of the eye to rule out intraocular causes.
    • If slit lamp examination is normal, administer low-dose pilocarpine (0.1%) or methacholine (2.5%) eye drops
      • If pupil constricts: suspect Adie tonic pupil
      • If pupil does not constrict: administer high-dose pilocarpine (1%) eye drops
        • If pupil does not constrict: suspect pharmacological mydriasis
        • If pupil constricts: suspect oculomotor nerve palsy
  • If the light reflex is adequate in both eyes, perform a slit lamp examination to look for a dilation lag.
    • If no dilation lag is present, administer cocaine (2–10%) or apraclonidine (0.5–1%) eye drops
      • If pupil does not dilate: Horner syndrome
    • If dilation lag is present, suspect Horner syndrome

Anisocoria is not associated with afferent pupillary defects.

• Gardener pupil: pupillary dilation (mydriasis) due to ingestion of plant alkaloids, e.g., of Jimson weed (Datura stramonium)
• Blown pupil: pupillary dilation (may be accompanied by ptosis) due to a saccular aneurysm: in the posterior communicating artery territory or uncal herniation causing compression of the ipsilateral oculomotor cranial nerve.
• Fixed dilated pupil: dilated, unresponsive pupil, e.g. due to closed-angle glaucoma
• Hutchinson pupil: pupillary abnormalities that lead to a fixed dilated pupil in 3 stages as a result of increased intracranial pressure (typically uncal herniation).
  • Stage 1: irritation of the ipsilateral parasympathetic fibers overlying the oculomotor nerve → constriction of the ipsilateral pupil
  • Stage 2
    • Compression of the ipsilateral parasympathetic fibers overlying the oculomotor nerve → dilation of the ipsilateral pupil
    • Irritation of the contralateral parasympathetic fibers overlying the oculomotor nerve → constriction of the contralateral pupil
  • Stage 3: compression of the contralateral parasympathetic fibers overlying the oculomotor nerve → dilation of the contralateral pupil → both sides are paralyzed → both pupils are fixed and dilated
• Light-near dissociation: a sluggish reaction of the pupil to light with accommodation intact ^[4]
  • Unilateral light-near dissociation
    • Adie tonic pupil: light-near dissociation due to postganglionic parasympathetic pupillomotor damage
    • Holmes Adie syndrome: Adie tonic pupil accompanied by photophobia, diminished deep tendon reflexes, and orthostatic hypotension
    • Varicella-zoster infection
    • Giant cell arteritis
    • Orbital trauma
  • Bilateral light near-dissociation
    • Parinaud syndrome (e.g., pinealoma, multiple sclerosis, obstructive hydrocephalus, midbrain stroke)
    • Argyll Robertson pupils (neurosyphilis)