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Pupil: Physiology and Abnormalities

The pupil is the space within the eye that permits light to project onto the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy. Anatomically located in front of the lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy, the pupil's size is controlled by the surrounding iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy. The pupil provides insight Insight Psychiatric Assessment into the function of the central and autonomic nervous systems. The afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology pathway for visual function starts from the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy and moves through the optic tracts and lateral geniculate nuclei, terminating in the visual cortex Visual cortex Area of the occipital lobe concerned with the processing of visual information relayed via visual pathways. Cerebral Cortex: Anatomy. Light stimulus is conducted by the parasympathetic system Parasympathetic system The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system. Autonomic Nervous System: Anatomy to the midbrain Midbrain The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems. Brain Stem: Anatomy, while psychosensory reaction is processed by the sympathetic system Sympathetic system The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. Autonomic Nervous System: Anatomy. Efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology pathways produce the appropriate response: miosis and mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma from the parasympathetic and sympathetic innervations, respectively. Pupillary disorders result from defects in areas of the visual afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology and efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology pathways. Presentation varies with pupillary size along with response to light and medication.

Last updated: 2 Jun, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Pupil

  • Opening in the center of the iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy
  • Space within the eye that allows light to enter and stimulate the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy

Adjacent structures

  • Cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy:
    • In front of the pupil 
    • Transparent structure that provides fixed refraction Refraction Refractive Errors to focus Focus Area of enhancement measuring < 5 mm in diameter Imaging of the Breast light onto the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy
    • Primary site of refraction Refraction Refractive Errors
  • Lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy: 
    • Behind the pupil 
    • Transparent structure that provides adjustable refraction Refraction Refractive Errors to focus Focus Area of enhancement measuring < 5 mm in diameter Imaging of the Breast light onto the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy
  • Iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy:
    • Surrounding the pupil 
    • Colored portion of the eye, composed of contractile smooth muscle to control the size of the pupil
    • Circular muscle group: 
      • Sphincter pupillae for contraction (miosis)
      • Innervation: parasympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification
    • Radial muscle group: 
      • Dilator pupillae for dilation ( mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma)
      • Innervation: sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification

Physiology of the Pupil

Visual pathway Visual pathway The primary visual pathway consists of a relay system, beginning at the retina, whose ganglion cell axons form the optic nerve. The optic nerve fibers from each eye hemidecussate in the optic chiasm (OC), with nasal fibers joining the temporal fibers of the contralateral nerve. Signals are then transmitted to the primary visual cortex of the occipital lobe. The Visual Pathway and Related Disorders

Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology pathway

From stimuli to the primary visual cortex Visual cortex Area of the occipital lobe concerned with the processing of visual information relayed via visual pathways. Cerebral Cortex: Anatomy:

  • Retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy
  • Optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions to optic tract Optic Tract Nerve fiber originating from the optic chiasm that connects predominantly to the lateral geniculate bodies. It is the continuation of the visual pathway that conveys the visual information originally from the retina to the optic chiasm via the optic nerves. The Visual Pathway and Related Disorders
    • Optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions: Axons Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Nervous System: Histology of the ganglion cells Ganglion Cells The Visual Pathway and Related Disorders converge, forming the optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions.
    • Optic chiasm Optic Chiasm The x-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. The Visual Pathway and Related Disorders: where hemidecussation of optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions fibers occurs
    • Optic tract Optic Tract Nerve fiber originating from the optic chiasm that connects predominantly to the lateral geniculate bodies. It is the continuation of the visual pathway that conveys the visual information originally from the retina to the optic chiasm via the optic nerves. The Visual Pathway and Related Disorders:
  • Lateral geniculate nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles (LGN): synaptic relay in the midbrain Midbrain The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems. Brain Stem: Anatomy
    • Majority of the fibers pass posteriorly → genico-calcarine tracts → terminate in the primary visual cortex Visual cortex Area of the occipital lobe concerned with the processing of visual information relayed via visual pathways. Cerebral Cortex: Anatomy
    • Minority of fibers pass into the superior colliculus Superior Colliculus The anterior pair of the quadrigeminal bodies which coordinate the general behavioral orienting responses to visual stimuli, such as whole-body turning, and reaching. Cranial Nerve Palsies and Edinger-Westphal nuclei (for parasympathetic innervation of the pupil).
Visual system

Diagram of the visual pathway Visual pathway The primary visual pathway consists of a relay system, beginning at the retina, whose ganglion cell axons form the optic nerve. The optic nerve fibers from each eye hemidecussate in the optic chiasm (OC), with nasal fibers joining the temporal fibers of the contralateral nerve. Signals are then transmitted to the primary visual cortex of the occipital lobe. The Visual Pathway and Related Disorders and the visual fields: light enters the eye, sending signals to the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy and through the optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions. The nasal fibers of each eye decussate at the optic chiasm Optic Chiasm The x-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. The Visual Pathway and Related Disorders, continuing to the optic tract Optic Tract Nerve fiber originating from the optic chiasm that connects predominantly to the lateral geniculate bodies. It is the continuation of the visual pathway that conveys the visual information originally from the retina to the optic chiasm via the optic nerves. The Visual Pathway and Related Disorders with the temporal fibers: right nasal fibers join the left temporal fibers (blue lines) and the left nasal fibers join the right temporal fibers (red lines). Neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission at the lateral geniculate nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles. Optic radiations connect the lateral geniculate nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles to the primary visual cortex Visual cortex Area of the occipital lobe concerned with the processing of visual information relayed via visual pathways. Cerebral Cortex: Anatomy of the occipital lobe Occipital lobe Posterior portion of the cerebral hemispheres responsible for processing visual sensory information. It is located posterior to the parieto-occipital sulcus and extends to the preoccipital notch. Cerebral Cortex: Anatomy where visual information is processed.

Image by Lecturio.

Parasympathetic innervation pathway (pupillary light reflex)

  • Light stimuli → starts the afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology pathway from the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy, with impulses going to the pretectal nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles (at the level of the superior colliculus Superior Colliculus The anterior pair of the quadrigeminal bodies which coordinate the general behavioral orienting responses to visual stimuli, such as whole-body turning, and reaching. Cranial Nerve Palsies)
  • Protection from increased light intensity by diminishing the amount of light entering the eye
  • Part of the “rest and digest” response
  • Efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology pathway:
    • 1st-order neuron 1st-order neuron Originates in the hypothalamus and descends to the first synapse in the cervical spinal cord, located at levels C8–T2 (also called the ciliospinal center of Budge). Horner Syndrome
      • Pretectal nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles projects bilaterally to the Edinger-Westphal nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles, where the efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology limb begins (preganglionic parasympathetic) → CN III parasympathetic fibers → ciliary ganglion 
    • 2nd-order neuron 2nd-order neuron Preganglionic pupillomotor fibers exit the spinal cord at T1, travel through the brachial plexus, over the lung apex, ascending to the superior cervical ganglion located near the angle of the mandible and the bifurcation of the common carotid artery. Horner Syndrome
      • From the ciliary ganglion (postganglionic) → short ciliary nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission on sphincter pupillae → miosis
  • Consensual light reflex Consensual Light Reflex Ophthalmic Exam:
    • Pretectal nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles supplies the Edinger-Westphal nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles bilaterally.
    • Shining light in 1 eye → bilateral constriction of the pupils (miosis)
Pupillary reflex pathways

Pupillary light reflex pathway: from light stimulation of the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy to the midbrain Midbrain The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems. Brain Stem: Anatomy. Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology pathway (red and blue lines): Left light stimulus goes from the left retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy to the optic chiasm Optic Chiasm The x-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. The Visual Pathway and Related Disorders to the optic tract Optic Tract Nerve fiber originating from the optic chiasm that connects predominantly to the lateral geniculate bodies. It is the continuation of the visual pathway that conveys the visual information originally from the retina to the optic chiasm via the optic nerves. The Visual Pathway and Related Disorders, ending at the ipsilateral pretectal nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles. The pretectal nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles supplies both left and right Edinger-Westphal nuclei. Yellow lines show impulse from both nuclei reaching both ciliary ganglia and resulting in bilateral miosis.

Image by Lecturio.

Sympathetic innervation pathway

  • Psychosensory or physical stimuli Physical stimuli Act of eliciting a response from a person or organism through physical contact. Angioedema (darkness) → sympathetic response, stimulating the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy and optic tracts to send signal to the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus
  • Part of the “fight or flight” response
  • Efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology pathway:
    • 3-neuron chain originating from the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus
    • 1st-order (central neuron): 
      • Neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology from the posterior hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy at C8–T2 (ciliospinal center of Budge) 
    • 2nd-order (preganglionic neuron): 
      • Passes out of the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy → cervical sympathetic chain (through the brachial plexus Brachial Plexus The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (c5-c8 and T1), but variations are not uncommon. Peripheral Nerve Injuries in the Cervicothoracic Region, over the lung apex) 
      • From the sympathetic chain (going superiorly) → superior cervical ganglion 
    • 3rd-order (postganglionic neuron): 
      • From the superior cervical ganglion → oculosympathetic pathway joins the ophthalmic division of the trigeminal nerve Trigeminal nerve The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. The 12 Cranial Nerves: Overview and Functions (CN V) 
      • Oculosympathetic fibers synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission on the dilator pupillae ( mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma) and superior tarsal muscle/Müller’s muscle (upper lid elevation).
Sympathetic innervation pathway

Image of the sympathetic innervation pathway:
1st-order neuron 1st-order neuron Originates in the hypothalamus and descends to the first synapse in the cervical spinal cord, located at levels C8–T2 (also called the ciliospinal center of Budge). Horner Syndrome: starts from the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus to the center of Budge ( spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy C8–T2)
2nd-order neuron 2nd-order neuron Preganglionic pupillomotor fibers exit the spinal cord at T1, travel through the brachial plexus, over the lung apex, ascending to the superior cervical ganglion located near the angle of the mandible and the bifurcation of the common carotid artery. Horner Syndrome: passes out of the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy going superiorly to the superior cervical ganglion
3rd-order neuron 3rd-order neuron Pupillomotor fibers ascend along the internal carotid artery and enter the cavernous sinus where it is in close relation with the abducens nerve (cranial nerve (CN) VI). These fibers enter the orbit with the ophthalmic branch (V1) of the trigeminal nerve (CN V) via the long ciliary nerves, which innervate the iris dilator and Müller muscles. Horner Syndrome: joins the trigeminal nerve Trigeminal nerve The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. The 12 Cranial Nerves: Overview and Functions and oculosympathetic fibers, synapses on the dilator pupillae and Müller’s muscle, causing mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma and eyelid opening.

Image by Lecturio.

Near response

Consists of 3 responses:

  • Convergence
    • Medial eye movement to track object
    • Oculomotor nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles stimulates contraction of bilateral medial rectus Medial rectus Orbit and Extraocular Muscles: Anatomy muscles.
  • Contraction of the ciliary muscles
    • Alteration of lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy shape to maintain focus Focus Area of enhancement measuring < 5 mm in diameter Imaging of the Breast on the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy
    • Initially, ciliary muscles are relaxed, with eyes focused on distant objects.
    • With near objects, parasympathetic pathway stimulates the ciliary muscles → lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy thickening → ↑ refractive power ( lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy accommodation Accommodation Refractive Errors)
  • Constriction of the pupils
    • Adjustment of light to focus Focus Area of enhancement measuring < 5 mm in diameter Imaging of the Breast on near objects
    • Parasympathetic pathway stimulates the sphincter pupillae.

Examination of the Pupil

Light and near response

  • Examination in dim light
    • Direct response: Pupil constricts on direct illumination.
    • Consensual response: constriction on illumination of the contralateral eye
    • Without light or in the dark: Pupils dilate. 
    • Abnormal response: Pupil fails to dilate to the dark or fails to constrict to light or accommodation Accommodation Refractive Errors (near response).
  • Note the speed of response:
    • 4 +: brisk response 
    • 3 +: a moderate response
    • 2 +: a small, slowed response
    • 1 +: represents a tiny/just visible response
    • 0: indicates unresponsive pupils

Pupil size

  • Normal: 2–4 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma (bright), 4–8 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma (dark)
  • Isocoria: same size of pupils
  • Anisocoria: difference in size of pupils

Swinging-flashlight test

  • In a dark room, the patient fixates on a distant object.
  • With light source below the line of sight, confirm pupils are isocoric.
  • Shift illumination after 3 seconds from one eye to the other.
  • Normal response:
    • Shine light in 1 eye → equal bilateral constriction
    • During transfer, there is dilation.
    • Swing light to other eye → similar equal bilateral constriction 
    • Expected in an intact retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy and/or optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions

Slit-lamp examination Slit-Lamp Examination Blepharitis

  • Examines the surface of the iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy and pupillary margin
  • Irregularities, raised lesion, and pigment abnormalities can be seen.

Pharmacologic tests

  • Pharmacologic agents (topical cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics, apraclonidine Apraclonidine Glaucoma, pilocarpine Pilocarpine A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. Cholinomimetic Drugs or hydroxyamphetamine) utilized to check pupillary reactivity
  • Work-up for Horner’s syndrome, tonic pupil Tonic Pupil A pupillary abnormality characterized by a poor pupillary light reaction, reduced accommodation, iris sector palsies, an enhanced pupillary response to near effort that results in a prolonged, ‘tonic’ constriction, and slow pupillary redilation. This condition is associated with injury to the postganglionic parasympathetic innervation to the pupil. Amyloidosis, or pharmacologic mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma

Disorders of the Afferent Pathway

Relative afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology pupillary defect

  • Also called Marcus Gunn pupil
  • Pathophysiology: caused by unilateral or asymmetrical disease of the optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions or retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy
  • Presentation:
    • Impaired direct pupillary reflex in the affected eye and impaired indirect pupillary reflex in the normal eye
  • Swinging-flashlight test:
    • Abnormal response: paradoxical dilation or weak constriction when light shines into the affected eye (Marcus Gunn pupil)
  • Associated conditions:
    • Optic neuritis Optic neuritis Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). Cranial Nerve Palsies 
    • Traumatic optic neuropathy Neuropathy Leprosy
    • Ischemic optic disease or retinal disease
    • Glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma causing optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions damage
    • Retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment
    • Severe macular degeneration Macular degeneration Age-related macular degeneration (AMD) is visual impairment due to changes in the macula, the area responsible for high-acuity vision. It is marked by central vision loss with peripheral vision relatively spared. Risk factors include advanced age, smoking, family history, and cardiovascular disease. Macular Degeneration
    • Retinitis ( cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus (CMV), herpes)
    • Optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions tumors
    • Other optic neuropathies Neuropathies Chédiak-Higashi Syndrome

Anisocoria

Physiologic anisocoria

  • Difference between the pupil size remains the same regardless of illumination.
  • Affects 20% of normal individuals 
  • Difference in size: typically < 1 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
  • No damage to the sphincter and dilator pupillae innervation
  • Normal pupillary reactions to light and darkness 
  • Review of old photographs Photographs Ultrasound (Sonography) or driver’s license helps with diagnosis.

Pathologic anisocoria

  • Pathophysiology:
    • Neural defect of the efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology pupillomotor pathways innervating the iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy muscles in 1 or both eyes Both Eyes Refractive Errors
    • Structural defect of 1 or both irides 
  • Presentation:
    • Pathologically small pupil: in darkness, usually remains small while the normal pupil dilates
    • Pathologically large pupil: in bright light, remains large while the normal pupil constricts
    • Difference usually > 1 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
  • Associated conditions:
    • Horner’s syndrome
    • CN III palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies with pupillary involvement
    • Adie tonic pupil Tonic Pupil A pupillary abnormality characterized by a poor pupillary light reaction, reduced accommodation, iris sector palsies, an enhanced pupillary response to near effort that results in a prolonged, ‘tonic’ constriction, and slow pupillary redilation. This condition is associated with injury to the postganglionic parasympathetic innervation to the pupil. Amyloidosis
    • Anterior uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea
    • Acute angle closure glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma
    • Trauma or surgery
    • Congenital Congenital Chorioretinitis defects ( coloboma Coloboma Congenital anomaly in which some of the structures of the eye are absent due to incomplete fusion of the fetal intraocular fissure during gestation. Esophageal Atresia and Tracheoesophageal Fistula or heterochromia iridis)
Evident right mydriasis

Anisocoria with right mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma

Image: “Evident right mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma” by U,O,C Pediatria Generale Dipartimento di DI Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of di: central di (CDI) and nephrogenic di (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus Medicina Pediatrica, Ospedale Pediatrico Bambino Gesù, Piazza Sant’Onofrio 4, 00165 Roma, Italy. License: CC BY 2.0

Disorders of the Efferent Pathway

Adie tonic pupil Tonic Pupil A pupillary abnormality characterized by a poor pupillary light reaction, reduced accommodation, iris sector palsies, an enhanced pupillary response to near effort that results in a prolonged, ‘tonic’ constriction, and slow pupillary redilation. This condition is associated with injury to the postganglionic parasympathetic innervation to the pupil. Amyloidosis

  • Large pupil, impaired light reaction
  • Presentation:
    • Tonic, usually unilateral mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma 
    • Has light-near dissociation Dissociation Defense Mechanisms
      • No or poor constriction on illumination 
      • Positive near response (constriction) but slow redilation
    • More common in women 30–40 years of age
    • Holmes-Adie syndrome: loss of deep tendon reflexes Deep Tendon Reflexes Neurological Examination
  • Pathophysiology: degeneration of the ciliary ganglion and postganglionic parasympathetic denervation of the affected pupil
  • Associated conditions:
    • Idiopathic Idiopathic Dermatomyositis (most cases)
    • Infection (viral or bacterial)
    • Trauma or surgery
    • Tumors
    • Ross syndrome: tonic pupil Tonic Pupil A pupillary abnormality characterized by a poor pupillary light reaction, reduced accommodation, iris sector palsies, an enhanced pupillary response to near effort that results in a prolonged, ‘tonic’ constriction, and slow pupillary redilation. This condition is associated with injury to the postganglionic parasympathetic innervation to the pupil. Amyloidosis, hyporeflexia Hyporeflexia Duchenne Muscular Dystrophy, sudomotor disturbances
  • Pilocarpine Pilocarpine A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. Cholinomimetic Drugs test:
    • Tonic pupil Tonic Pupil A pupillary abnormality characterized by a poor pupillary light reaction, reduced accommodation, iris sector palsies, an enhanced pupillary response to near effort that results in a prolonged, ‘tonic’ constriction, and slow pupillary redilation. This condition is associated with injury to the postganglionic parasympathetic innervation to the pupil. Amyloidosis
      • Has cholinergic supersensitivity
      • Will constrict; more miotic response than normal pupil
Tonic right pupil

Tonic right pupil: unresponsive to light stimulation

Image: “Holmes-Adie’s Syndrome” by US National Library of Medicine. License: CC BY 4.0

Argyll Robertson pupil

  • Small bilateral pupils, impaired light reaction
  • Presentation:
  • Pathophysiology: result of dorsal midbrain Midbrain The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems. Brain Stem: Anatomy lesion (damages nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology that control pupillary reflex but spares more ventral nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology that control accommodation reflex Accommodation Reflex The dioptric adjustment of the eye (to attain maximal sharpness of retinal imagery for an object of regard) referring to the ability, to the mechanism, or to the process. Ocular accommodation is the effecting of refractive changes by changes in the shape of the crystalline lens. Loosely, it refers to ocular adjustments for vision, ocular at various distances. Cranial Nerve Palsies)
  • Associated with late-stage syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis:
    • Other symptoms: sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia and lancinating pains in tabes dorsalis Tabes dorsalis Parenchymatous neurosyphilis marked by slowly progressive degeneration of the posterior columns, posterior roots, and ganglia of the spinal cord. The condition tends to present 15 to 20 years after the initial infection and is characterized by lightning-like pains in the lower extremities, urinary incontinence; ataxia; severely impaired position and vibratory sense, abnormal gait, optic atrophy; Argyll-Robertson pupils, hypotonia, hyperreflexia, and trophic joint degeneration. Syphilis
    • Treatment: penicillin Penicillin Rheumatic Fever regimen for neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis
Argyll robertson pupil

Argyll Robertson pupil with bilateral miosis that do not constrict to light, but do constrict to accommodation Accommodation Refractive Errors

Image by Lecturio.

Horner’s syndrome

  • Small pupil, normal light reaction
  • Anisocoria more noted in the dark (abnormal pupil with dilation lag)
  • Presentation:
    • Ptosis Ptosis Cranial Nerve Palsies: paresis Paresis A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. ‘general paresis’ and ‘general paralysis’ may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. Spinal Disk Herniation of Müller’s muscle
    • Anhidrosis: damage proximal to fibers mediating sweat and temperature
    • Miosis: loss of innervation to dilator pupillae 
  • Pathophysiology: results from disruption of sympathetic chain 
  • Associated conditions:
    • 1st-order neuron 1st-order neuron Originates in the hypothalamus and descends to the first synapse in the cervical spinal cord, located at levels C8–T2 (also called the ciliospinal center of Budge). Horner Syndrome: lateral medullary syndrome Lateral Medullary Syndrome Lateral medullary syndrome (also known as Wallenberg syndrome, posterior inferior cerebellar artery (PICA) syndrome, and vertebral artery syndrome) is a neurological constellation of symptoms and signs due to obstruction in vessels supplying the medulla, resulting in brainstem ischemia or infarction. Lateral Medullary Syndrome (Wallenberg Syndrome) (Wallenberg’s syndrome) or tumors or strokes affecting 1st-order sympathetic tract 
    • 2nd-order neuron 2nd-order neuron Preganglionic pupillomotor fibers exit the spinal cord at T1, travel through the brachial plexus, over the lung apex, ascending to the superior cervical ganglion located near the angle of the mandible and the bifurcation of the common carotid artery. Horner Syndrome: trauma or tumors in spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy, thoracic outlet Thoracic Outlet Thoracic Outlet Syndrome, or lung apex (Pancoast tumor Tumor Inflammation)
    • 3rd-order neuron 3rd-order neuron Pupillomotor fibers ascend along the internal carotid artery and enter the cavernous sinus where it is in close relation with the abducens nerve (cranial nerve (CN) VI). These fibers enter the orbit with the ophthalmic branch (V1) of the trigeminal nerve (CN V) via the long ciliary nerves, which innervate the iris dilator and Müller muscles. Horner Syndrome: carotid dissection Carotid dissection Carotid and vertebral artery dissections occur when the integrity of the arterial wall structure fails, usually abruptly, resulting in intramural hematoma formation and a false lumen between the tunica media and the intimal or adventitial layers. This may result in aneurysm, stenosis, or occlusion. Dissection of the Carotid and Vertebral Arteries, thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus, cavernous sinus aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms
  • Pharmacologic tests:
    • Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics solution: 
      • Blocks reuptake of norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS and dilates the eye with intact sympathetic innervation  
      • Horner’s syndrome: poor-to-no dilation (impaired sympathetic innervation)
    • Apraclonidine Apraclonidine Glaucoma (0.5%–1% solution):
      • A weak alpha-1 agonist and strong alpha-2 agonist
      • Horner’s syndrome (dominant supersensitivity to alpha-1 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors): Affected pupil dilates. 
    • Localization with topical hydroxyamphetamine:
      • Hydroxyamphetamine releases norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS from intact postganglionic fibers (this test helps to localize the lesion).
      • Horner’s syndrome with intact postganglionic fibers: dilate affected pupil ≥ normal pupil
      • Horner’s syndrome with damaged postganglionic fibers: no pupil dilation

Pharmacology and Pupillary Effects

Table: Pupillary effects of medications
Medication Mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma Miosis
Ophthalmic medications
  • Anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs
    • Atropine Atropine An alkaloid, originally from atropa belladonna, but found in other plants, mainly solanaceae. Hyoscyamine is the 3(s)-endo isomer of atropine. Anticholinergic Drugs
    • Cyclopentolate Cyclopentolate A parasympatholytic anticholinergic used solely to obtain mydriasis or cycloplegia. Anticholinergic Drugs
  • Mydriatic
    • Tropicamide Tropicamide One of the muscarinic antagonists with pharmacologic action similar to atropine and used mainly as an ophthalmic parasympatholytic or mydriatic. Anticholinergic Drugs
  • Alpha-adrenergic agonist
  • Miotic/anti-glaucoma
    • Pilocarpine Pilocarpine A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. Cholinomimetic Drugs
    • Carbachol Carbachol A slowly hydrolyzed cholinergic agonist that acts at both muscarinic receptors and nicotinic receptors. Cholinomimetic Drugs
  • Anticholinesterase
    • Physostigmine Physostigmine A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. Cholinomimetic Drugs
Illicit drugs Illicit Drugs Drugs that are manufactured, obtained, or sold illegally. They include prescription drugs obtained or sold without prescription and non-prescription drugs. Illicit drugs are widely distributed, tend to be grossly impure and may cause unexpected toxicity. Delirium
  • Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics
  • Amphetamine
  • Lysergic acid diethylamide (LSD)
Heroin Heroin A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of federal regulations, title 21 parts 329. 1, 1308. 11 (1987). Sale is forbidden in the United States by federal statute. Nephrotic Syndrome
Other medications
  • Antihistamine
    • Diphenhydramine Diphenhydramine A histamine h1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. Antihistamines
  • Anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs
    • Ipratropium Ipratropium A muscarinic antagonist structurally related to atropine but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic. Anticholinergic Drugs
    • Scopolamine Scopolamine An alkaloid from solanaceae, especially datura and scopolia. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Its many uses include an anesthetic premedication, the treatment of urinary incontinence and motion sickness, an antispasmodic, and a mydriatic and cycloplegic. Antiemetics
  • Tricyclic antidepressant Antidepressant Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressants
    • Desipramine Desipramine A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors. Tricyclic Antidepressants
  • Anti-Parkinson’s
    • Carbidopa-levodopa
Opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation
  • Morphine Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Opioid Analgesics
  • Codeine Codeine An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. Opioid Analgesics
  • Hydrocodone Hydrocodone Opioid Analgesics
Herbal Jimsonweed (with anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs properties)

Differential Diagnosis

  • Glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma: an optic neuropathy Neuropathy Leprosy with distinctive changes in the optic cup and visual field Visual Field The Visual Pathway and Related Disorders defect. Glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma is often associated with increased pressure within the eyeball (commonly within the anterior and posterior chambers), which results in gradual vision Vision Ophthalmic Exam loss. This can occur acutely due to a blockage of the aqueous humor Aqueous humor The clear, watery fluid which fills the anterior and posterior chambers of the eye. It has a refractive index lower than the crystalline lens, which it surrounds, and is involved in the metabolism of the cornea and the crystalline lens. Eye: Anatomy drainage (acute angle-closure glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma) and presents as a mid-dilated pupil. Diagnosis is critical, as acute angle-closure glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma is an emergency. Gonioscopy Gonioscopy Examination of the angle of the anterior chamber of the eye with a specialized optical instrument (gonioscope) or a contact prism lens. Glaucoma is utilized to visualize the angle. Treatment of choice is peripheral iridotomy.
  • Multiple sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor ( MS MS Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis): a chronic inflammatory autoimmune demyelinating disease of the central nervous system Central nervous system The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Nervous System: Anatomy, Structure, and Classification. Multiple sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor causes acute demyelinating optic neuropathy Neuropathy Leprosy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship report acute-to-subacute vision Vision Ophthalmic Exam loss with pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways on eye movements. Detection of relative afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology pupillary defect (RAPD) is suggestive of optic neuropathy Neuropathy Leprosy. Internuclear ophthalmoplegia Ophthalmoplegia Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. Orbital and Preseptal Cellulitis can also result from MS MS Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis, exhibited as diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis, nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism, and loss of depth perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment. Magnetic resonance imaging helps detect the demyelinating plaques on the affected nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification. Treatment involves immunomodulation and symptomatic relief.
  • 3rd nerve palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies: neurologic deficit characterized by a large, sluggishly reactive to unreactive pupil, ptosis Ptosis Cranial Nerve Palsies, and paralysis of eye movement ( adduction Adduction Examination of the Upper Limbs, elevation, and depression) resulting from lesions along its path from the oculomotor nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles in the midbrain Midbrain The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the pons and the diencephalon. Midbrain contains two major parts, the dorsal tectum mesencephali and the ventral tegmentum mesencephali, housing components of auditory, visual, and other sensorimotor systems. Brain Stem: Anatomy to the orbit Orbit The orbit is the cavity of the skull in which the eye and its appendages are situated. The orbit is composed of 7 bones and has a pyramidal shape, with its apex pointed posteromedially. The orbital contents comprise the eye, extraocular muscles, 5 cranial nerves, blood vessels, fat, the lacrimal apparatus, among others. Orbit and Extraocular Muscles: Anatomy. Causes include aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms, ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, and trauma. Magnetic resonance imaging with angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery helps evaluate the etiology. Treatment is directed toward the underlying condition causing the palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies.
  • Retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment: separation of the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy from the retinal pigment epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology resulting in rapid photoreceptor damage. Symptoms include painless vision Vision Ophthalmic Exam changes such as sudden flashes of light, floaters Floaters Chorioretinitis, worsening peripheral vision Vision Ophthalmic Exam, or having a shadow in the field of vision Vision Ophthalmic Exam. Vision Vision Ophthalmic Exam is described as curtain-like. Macular involvement would present as rapid afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology pupillary defect due to photoreceptor degeneration caused by the detachment. Acute visual loss from retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment is an emergency requiring corrective surgery.
  • Hutchinson’s pupil: dilated pupil that occurs due to compression Compression Blunt Chest Trauma of the ipsilateral 3rd cranial nerve arising from trauma, tumor Tumor Inflammation, or aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms. Irritation on the nerve initially leads to pupillary constriction of the affected eye. As the nerve is mechanically compressed, the superficially located parasympathetic nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology on the oculomotor nerve Oculomotor nerve The 3D cranial nerve. The oculomotor nerve sends motor fibers to the levator muscles of the eyelid and to the superior rectus, inferior rectus, and inferior oblique muscles of the eye. It also sends parasympathetic efferents (via the ciliary ganglion) to the muscles controlling pupillary constriction and accommodation. The motor fibers originate in the oculomotor nuclei of the midbrain. The 12 Cranial Nerves: Overview and Functions are paralyzed, so isolated mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma follows. Further increases in intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension leads to bilateral pupillary dilation. This dilation is associated with uncal herniation Uncal Herniation Increased Intracranial Pressure (ICP). Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification imaging is necessary to determine etiology.

References

  1. American Academy of Ophthalmology. Pupillary examination. Retrieved 9 Oct 2020, from https://www.aao.org/bcscsnippetdetail.aspx?id=ce5e4e47-1d5f-4a06-b1c9-22c23879114a
  2. Belliveau, A., Somani, A., Dossani R. (2020) Pupillary light reflex. StatPearls. Retrieved 10 Oct 2020, from https://www.ncbi.nlm.nih.gov/books/NBK537180/#_NBK537180_pubdet_  
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  7. Kedar, S., Biousse, V., Newman, N. (2018). Horner Syndrome. UpToDate. Retrieved 11 Oct 2020, from https://www.uptodate.com/contents/horner-syndrome
  8. LaRoche, M. (2017). Anisocoria and an Array of Neurologic Symptoms in an Adult with Ewing Sarcoma. Journal of the Advanced Practitioner in Oncology 8 (1). https://www.researchgate.net/publication/313146824_Anisocoria_and_an_Array_of_Neurologic_Symptoms_in_an_Adult_With_Ewing_Sarcoma
  9. Motlagh, M., Geetha, R. (2020). Physiology, Accommodation. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK542189/
  10. Somani, A., Kini, A. Lee, A. Othman, B., Zenden,J., Ponce, C. (2020) Reflexes and the Eye. https://eyewiki.aao.org/Reflexes_and_the_Eye#cite_note-:1-2
  11. Spector, R. (1990). The Pupils. https://www.ncbi.nlm.nih.gov/books/NBK381/
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