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Pupillary Disorders LAURA J 13 Pupillary Disorders LAURA J. BALCER Pupillary disorders usually fall into one of three major cat- cortex generally do not affect pupillary size or reactivity. egories: (1) abnormally shaped pupils, (2) abnormal pupillary Efferent parasympathetic fibers, arising from the Edinger– reaction to light, or (3) unequally sized pupils (anisocoria). Westphal nucleus, exit the midbrain within the third nerve Occasionally pupillary abnormalities are isolated findings, (efferent arc). Within the subarachnoid portion of the third but in many cases they are manifestations of more serious nerve, pupillary fibers tend to run on the external surface, intracranial pathology. making them more vulnerable to compression or infiltration The pupillary examination is discussed in detail in and less susceptible to vascular insult. Within the anterior Chapter 2. Pupillary neuroanatomy and physiology are cavernous sinus, the third nerve divides into two portions. reviewed here, and then the various pupillary disorders, The pupillary fibers follow the inferior division into the orbit, grouped roughly into one of the three listed categories, are where they then synapse at the ciliary ganglion, which lies discussed. in the posterior part of the orbit between the optic nerve and lateral rectus muscle (Fig. 13.3). The ciliary ganglion issues postganglionic cholinergic short ciliary nerves, which Neuroanatomy and Physiology initially travel to the globe with the nerve to the inferior oblique muscle, then between the sclera and choroid, to The major functions of the pupil are to vary the quantity of innervate the ciliary body and iris sphincter muscle. Fibers light reaching the retina, to minimize the spherical aberra- to the ciliary body outnumber those to the iris sphincter tions of the peripheral cornea and lens, and to increase the muscle by 30 : 1. depth of field (the depth within which objects will appear The near response consists of pupillary constriction, accom- sharp). In most individuals the two pupils are equal in size, modation (change in the shape of the lens), and convergence and each is situated slightly nasal and inferior to the center of the eyes (see Chapter 2). Although the pathways are of the cornea and iris (Fig. 13.1). uncertain, the supranuclear control for the near response The iris contains the two muscles that control the size of likely arises from diffuse cortical locations. Stimulation of the pupil. Contraction of the dilator muscle leads to pupillary the peristriate cortex (areas 19 and 22) in primates can evoke enlargement (mydriasis), while sphincter muscle contraction a near response,5 but more recent evidence suggests the causes pupillary constriction (miosis). The sphincter muscle lateral suprasylvian area is also related to the control of lens wraps 360 degrees around the pupillary margin, and the accommodation.6 The signals converge in the rostral superior dilator muscle similarly encircles the pupil but is more periph- colliculus, near which a group of midbrain near-response erally located. neurons coordinates the pretectum for accommodation and Normally, light directed at either eye leads to bilateral miosis, the mesencephalic reticular formation for accom- pupillary constriction, and this pupillary light reflex is medi- modation and vergence, and the raphe interpositus for visual ated by a parasympathetic pathway (see Fig. 13.2 for details). fixation.6,7 The final signal for pupillary miosis during near Light entering the eye causes retinal photoreceptors to hyper- viewing is still mediated by the Edinger–Westphal nuclei. polarize, in turn causing activation of retinal interneurons Pupillary dilation is the function of the oculosympathetic and ultimately the retinal ganglion cells. Additionally, intrin- system (the ocular part of the sympathetic nervous system), sically photosensitive retinal ganglion cells (ipRGCs) contain- which consists of three neurons beginning in the postero- ing melanopsin, a photopigment, can be activated by light lateral hypothalamus and ending at the iris and eyelids (see without photoreceptor input.1,2 The ipRGCs are most sensitive Fig. 13.4 for details). The first-order neuron projects from to blue light, and the preservation of circadian rhythms and the hypothalamus through ill-defined brainstem pathways the pupillary light reflexes in patients with severe photore- to synapse on the intermediolateral cell column in the spinal ceptor diseases and Leber’s hereditary optic neuropathy can cord at C8–T2 (ciliospinal center of Budge). The second-order be explained by intact ipRGC function.3,4 neuron (preganglionic) leaves the spinal cord and travels Retinal ganglion cell axons activated by photoreceptors over the apex of the lung before ascending with the internal and ipRGCs together mediate the pupillary light reflex and carotid artery to synapse at the superior cervical ganglion. travel through the optic nerve, chiasm, and optic tract to In the region of the lung apex, the sympathetic pathway lies reach the pretectal nuclei (afferent arc). Interneurons then in close proximity to the lower brachial plexus. The third- connect the pretectal nuclei to the Edinger–Westphal nuclei. order neuron (postganglionic) travels along the internal Although these connections are bilateral, the input into the carotid into the cavernous sinus, after which the sympathetic Edinger–Westphal nuclei is predominantly from the contra- pathways follow the sixth nerve, then the nasociliary nerve lateral pretectal nucleus. Since the afferent pupillary fibers (a branch of the first division of the trigeminal nerve), then leave the optic tract before the lateral geniculate nucleus, the long ciliary nerve into the orbit.8 This neuron releases isolated lesions of the geniculate, optic radiations, and visual the neurotransmitter norepinephrine at the iris dilator muscle. 417 Downloaded for Anonymous User (n/a) at The Pennsylvania State University from ClinicalKey.com by Elsevier on June 21, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. 418 PART 3 • Efferent Neuro-Ophthalmic Disorders SC PTN LGN E–W III OT CHI Figure 13.1. A normal left eye. Note the pupil is slightly nasal to the center of the cornea and iris. CG Pharmacologic Testing ON of the Pupils RET As will be discussed, pharmacologic testing helps confirm the clinical diagnosis of many pupillary abnormalities. Some general guidelines need to be followed in this regard. By dis- rupting the corneal epithelium, corneal reflex evaluation and applanation or pneumotonometry may alter corneal permeability of the drug and therefore should not be per- Figure 13.2. Pupillary light reflex—parasympathetic pathway. Light formed on the same day as pharmacologic testing. In general, entering one eye (straight dark arrow, bottom right) stimulates the retinal photoreceptors (RET), resulting in excitation of ganglion cells, whose the drops should be instilled in the inferior cul-de-sac, with axons travel within the optic nerve (ON), partially decussate in the chiasm care taken to use the same size drop in each eye. Drop admin- (CHI), then leave the optic tract (OT) (before the lateral geniculate nucleus istration should be repeated 1–5 minutes later. The pupil (LGN)) and pass through the brachium of the superior colliculus (SC) sizes then can be measured 30–45 minutes after instillation before synapsing at the mesencephalic pretectal nucleus (PTN). This of the last set of drops. Baseline and test pupillary sizes are structure connects bilaterally, but predominantly contralaterally, to the oculomotor nuclear complex at the Edinger–Westphal (E-W) nuclei, best measured in the same lighting conditions, and photo- which issue parasympathetic fibers that travel within the third nerve graphic documentation before and after testing can be helpful. (inferior division) and terminate at the ciliary ganglion (CG) in the orbit. Postsynaptic cells innervate the pupillary sphincter, resulting in miosis. Light in one eye causes bilateral pupillary constriction. Pupillometry: an Additional Tool Pupillometry, the computerized measurement of pupillary responses to light stimulation, can be used to characterize Box 13.1 Causes of Abnormally Shaped Pupils relative afferent pupillary defects (RAPDs) objectively in patients 9–11 with or without vision loss. In addition, pupillometry has Congenital Causes been used in the intensive care setting to document abnor- Aniridia malities in pupillary reactivity related to increases in intra- Ectopia lentis et pupillae 12,13 cranial pressure in patients with traumatic brain injury. Iris coloboma Anterior chamber cleavage anomalies Ectopic pupils Abnormally Shaped Pupils Persistent pupillary membranes Acquired Causes Irregularly shaped pupils may be congenital or acquired (Box 13.1). Congenital conditions include the following: Iritis Iridocorneal endothelial syndrome Trauma (accidental or surgical) 1. Aniridia, in which the iris is hypoplastic, creating a large Iris atrophy (e.g., diabetes, herpetic disease) pupillary opening. Associated ocular findings often Neurologic (e.g., tonic pupils, midbrain damage (corectopia), include cataracts, glaucoma, and impaired vision due to tadpole-shaped pupils) macular or optic nerve hypoplasia. Patients with aniridia, Downloaded for Anonymous User (n/a) at The Pennsylvania State University from ClinicalKey.com by Elsevier on June 21, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. 13 • Pupillary
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