Anisokoria

• Ketidaksamaan lebar pupil antara kedua mata dengan pebedaan 0,4mm atau lebih

• Anisokoria patologis terjadi karena defek aferen parasimpatis atau simpatis pada satu mata atau dua mata secara asimetris

• Anisokoria lebih nyata pada keadaan gelap kelemahan otot dilator pupil atau saraf simpatis pada mata yang pupilnya tidak mau lebar

• Anisokoria lebih nyata pada keadaan terang kelemahan sfingter pupil atau parasimpatis pada mata yang pupilnya tidak mau mengecil

Anisocoria with normally reactive pupils• Differential diagnosis •• – physiologic anisocoria • – Horner’s syndrome • - intermittent pupillary mydriasis of young (some cases)

Physiologic anisocoria• • present in 15–20% of normal people • • present at birth • • may be very obvious or very subtle • • may change both size and side by hour • • no visual effects • • if the patient is asymptomatic and there is normal motility

and no ptosis, no pharmacologic testing or other investigations are required

• • occasionally, however, if by coincidence there is a mild ptosis of another cause, there can be concern that the patient could have Horner’s syndrome

• pharmacologic testing to differentiate physiologic anisocoria from Horner’s syndrome: • – the transmitter substance at the neuromuscular junction of the

sympathetic pathway is norepinephrine • – 10% cocaine blocks the reuptake of norepinephrine • – patients with physiologic anisocoria have normal release of

norepinephrine at the junction of the sympathetic neuron and the iris dilator

• – a patient with physiologic anisocoria will show dilation of both pupils 45 minutes after 2 drops of 10% cocaine are instilled in both eyes (compared with Horner’s syndrome in which there is no dilation)

Horner’s syndrome

• anisocoria with smaller pupil on side of lesion • pupils normally reactive to light (actually, Horner’s pupil is hyperreactive to light) • ipsilateral upper eyelid ptosis (from involvement of Muller muscle) • upside-down ptosis of ipsilateral lower lid (lower lid slightly higher) • apparent enophthalmos (from ptosis of upper and lower lids)

Pharmacologic testing to confirm the diagnosis of Horner’s syndrome

• regardless of the location of the lesion along the sympathetic pathway, patients with Horner’s syndrome have a reduced rate of norepinephrine release at the iris dilator neuromuscular junction • 10% cocaine will not dilate a Horner’s pupil (or will dilate it minimally) • place two drops of 10% cocaine in each eye • place cocaine in the eye with the smaller pupil first – why? Because topical cocaine is a major ocular irritant. If cocaine drops are put in the eye with the larger pupil first, the patient may squeeze the lids tightly while you are trying to put drops in the other eye. Then, if the smaller pupil fails to dilate, it could be because it is a Horner’s pupil OR because the drops didn’t get into the eye because of squeezing of the eyelids. If the cocaine drops are placed first in the eye with the smaller pupil, the latter argument cannot be made • wait 45 minutes • examine the pupils in dim light or a dark room – why? Because cocaine affects only the sympathetic system, not the parasympathetic system. If the pupils are examined in bright light, they may constrict and the effects of the cocaine may not be appreciated

• why bother with a cocaine test if the patient has anisocoria and ipsilateral ptosis? – because 15–20% of normal people have physiologic anisocoria and if such a patient has unilateral ptosis from another condition (e.g. age-related levator dehiscence), there is a 50% chance that the ptosis and the miotic pupil will be on the same side • is there an alternative to the cocaine test? – cocaine drops may be hard or impossible to obtain – one can use apraclonidine instead – apraclonidine is an alpha-adrenergic receptor agonist – it reduces aqueous production and lowers IOP – a 1% solution will dilate a Horner’s pupil (1.0–4.5 mm), with no change in the normal pupil (often reversing anisocoria!) – a 0.5% solution will work just as well

• central (first order) – head or neck – brainstem stroke – brainstem tumor – spinal cord tumor – cervical spondylosis

• preganglionic (second order) – neck or chest – apical lung tumor– internal carotid artery dissection – iatrogenic (from neck or chest surgery)

• postganglionic (third order) – head or neck – internal carotid artery dissection – cavernous sinus tumor or inflammation – Raeder paratrigeminal neuralgia – iatrogenic (neck surgery)

Pharmacologic testing to determine the location of the lesion• paredrine (1% hydroxyamphetamine) stimulates release of norepinephrine from the presynaptic portion of the neuromuscular junction; it

– dilates a normal pupil – dilates central and preganglionic Horner’s pupils

– will not dilate a postganglionic Horner’s • phenylephrine (1%) will dilate a postganglionic Horner’s

syndrome (due to denervation sensitivity) but not a preganglionic Horner’s syndrome

Summary of pharmacologic testing for Horner’s syndrome

Investigations

• central or preganglionic – cervical spine films in flexion and extension – chest CT scan – MRI brain (with detailed views of brainstem); MRI/MRA or CT/CTA of neck • postganglionic – MRI brain (with detailed views of skull base and cavernous sinus); MRI/MRA of neck

Anisocoria with one pupil that is poorly reactive or non-reactive to light

•Differential diagnosis • iris sphincter damage (traumatic mydriasis) • pharmacologic blockade • tonic pupil • third nerve palsy • intermittent unilateral pupillary mydriasis (parasympathetic form)

Evaluation• perform slit-lamp examination to look for iris sphincter damage • check for other evidence of third nerve paresis (e.g. ptosis, exodeviation, hyper- or hypotropia or phoria) • the diagnosis is usually clinically apparent. However, in a minority of cases pharmacologic testing is required: – use 1% pilocarpine for a widely dilated, non-reactive pupil (possible pharmacologic dilation) – use 1% tropicamide for a markedly constricted, non-reactive pupil (possible pharmacologic constriction) – use 0.1% pilocarpine for a moderately dilated pupil with sector paralysis, vermiform movements or light-near dissociation with tonic redilation (possible tonic pupil)

Iris sphincter damage (traumatic mydriasis)• pupil usually irregularly dilated• some reaction usually present • easily detected using slit-lamp biomicroscopy

Pharmacologic blockade• Topical parasympatholytic agents (causing dilated pupil/s)

– atropine – scopolamine (patch for seasickness/postoperative nausea) – anticholinergic nasal sprays (inhalants) – ipratropium bromide (e.g. in Atrovent) – plants, e.g. datura (cornpicker’s pupil)

• testing for parsympatholytic pharmacologic blockade: – place two drops of 1% pilocarpine in each lower cul-de-sac – wait 45 minutes and observe – anything less than full constriction is a positive test for pharmacologic blockade

Pharmacologic blockade• Topical parasympathomimetic agents (causing constricted

pupil/s) • organophosphate pesticide (causes non-reactive miotic pupil) • testing for parasympathomimetic pharmacologic blockade: – place two drops of 1% tropicamide in each lower cul-de-sac – wait 45 minutes and observe – anything less than full dilation is a positive test for pharmacologic blockade

Tonic pupil

• dilated pupil • sluggish or no reaction to light • sluggish or no reaction to near (but when present, reaction to near better than to light) • slow redilation after constriction (very important) • sector iris paralysis • vermiform movements of iris • constricts to 0.1% pilocarpine

Etiology• features based on:

– number of fibers for pupillary constriction versus accommodation in the ciliary ganglion – aberrant regeneration in the peripheral nervous system– denervation supersensitivity

• number of fibers for pupillary constriction versus accommodation in the ciliary ganglion – about 95% of fibers in the ciliary ganglion are for accommodation – accommodation is more likely to be spared in ciliary ganglion damage – regeneration more likely to occur from fibers destined for ciliary body for accommodation • aberrant regeneration – after injury to a peripheral nerve, both injured and uninjured fibers regenerate – fibers originally intended for the ciliary body may regenerate to the iris sphincter; the pupil will constrict during near viewing but not to light • denervation supersensitivity – an organ deprived of its postganglionic nerve supply becomes supersensitive to the transmitter substance – the iris sphincter becomes supersensitive to acetylcholine and similar substances (e.g. pilocarpine) – once constriction of the pupil is achieved, supersensitivity of the iris sphincter prevents normal, rapid redilation

Causes• classification of tonic pupil syndromes

– local – with systemic or neurologic dysfunction – Adie’s (Holmes–Adie) syndrome

• local tonic pupils – tumor – trauma – inflammation (especially herpes zoster) – iatrogenic (lateral orbital exploration) – amyloid

• systemic/neuropathic tonic pupils – more often bilateral than other syndromes – diabetes mellitus – myotonic dystrophy – dysautonomic syndromes – Riley–Day – Shy–Drager – acute pandysautonomia – HIV autonomic neuropathy – paraneoplastic

Causes

• Adie’s (Holmes–Adie) syndrome – usually unilateral (4% become bilateral each year) – women more often affected than men (5:1) – usually occurs in early adulthood or middle age (20–50 years) – accommodation reduced or absent – absent deep tendon reflexes in 50–75% – natural history is for pupil to become smaller and

accommodation to improve – etiology unknown: possibly viral or autoimmune

Pharmacologic testing for tonic pupil• In most cases of tonic pupil, the diagnosis is obvious clinically

and no pharmacologic testing is required. However, if the diagnosis is unclear, dilute pilocarpine testing can be performed: • place two drops of 0.1% pilocarpine in lower cul-de-sac of each eye • wait 45 minutes and assess • tonic pupil will constrict (markedly) • normal pupil will not constrict • some third nerve palsy pupils will also constrict to this strength of pilocarpine – why? It is thought that some efferent pupillomotor fibers either bypass the ciliary ganglion or pass through it without synapsing

Third nerve palsy• Isolated anisocoria from third nerve palsy:

• the pupil is never widely dilated and non-reactive • in a patient with a mildly dilated, less reactive pupil – ask about episodic eyelid droop or diplopia – check position of lids – test for exodeviation on gaze toward opposite side – test for ipsilateral hypotropia in upgaze and

hypertropia in downgaze

Intermittent unilateral pupillary mydriasis (parasympathetic form)• one pupil transiently becomes large and poorly reactive to light • may be associated with migraine or occur as an isolated event, usually in young adults • even when not associated with migraine, 50% of patients have a history of migraines • poor reaction of the dilated pupil and reduced (or absent) accommodation • no ocular motor dysfunction or ptosis • lasts 15 minutes to several hours • MRI may show enhancement of the third nerve