The Pupillary Light Reflex Pathway: Afferent & Efferent Anisocoria ~ Now What?

Richard Mangan, OD, FAAO Eye Center of Richmond Adjunct Faculty, IU School of Optometry

Review of Anatomy Parasympathetic Pathway

„ Light stimulates the retina then impulse „ Iris sphincter travels with the ganglion cells through „ Iris dilator the chiasm into the oppgtic tracts. 80% go „ Parasympathetic to the LGN , 20% to the pretectal pathway nuclei.They then hemidecussate and „ Sympathetic pathway terminate at the EW nucleus

Parasympathetic Pathway „ Four neuron arc

„ Retina to the pretectal nucleus in the midbrain (1) „ Pretectal nucleus to the EW nucleus (2) „ EW nucleus to the ciliary ganglion (3) „ Ciliary ganglion to the iris sphincter with short ciliary nerves (4)

1 Points of Interest Sympathetic Pathway

„ Within the second order neuron there „ Three Neuron Arc are 30 near response fibers for every liggpht response fiber. This allows for li ght „ Posterior hypothalamus - near dissociation. to ciliospinalcenter of Budge (C8-(C8-T2)T2) „ The third order neuron runs with cranial „ CSCB to Sup. Cervical nerve III from the brain stem to the Ganglion in the neck ciliary ganglion. Superficially located „ SCG to the dilator muscle prior to the cavernous sinus.

Pupil Examination… …Be Systematic Pupil Examination „ What are the BCVA’s? …And are the acuities equal either corrected or with pinhole? Basics „ Are the patients pupils equal in size in bright and dim illumination? „ If not, is the anisocoria > in dim or bright illumination? „ Is the near accommodative reflex present and equal in both eyes? „ Are the accommodative amps = OU?

Pupil Examination (Cont.)

„ If the pupils are equal in size, is the direct light reflex equally strong in both eyes? „ Is the consensual light reflex equally strong in both eyes?

2 APD VIDEO

True or False? YES or NO?

„ A Cataract can cause and APD? „ Is it possible to have optic nerve disease and NOT have an APD?

„ FALSE… If you are finding an APD , check your illumination source first. „ YES…if the disease is bilateral & EQUAL „ If you still have a + APD, need to find in BOTH eyes (I.e., toxic optic other cause. neuropathy)

True or False? True or False?

„ Macular Degeneration can cause an „ Visual Acuity does not necessarily APD? correlate with an RAPD?

„ TRUE…If the Macular Degeneration is „ TRUE…a person with endend--stagestage unilateral & severe enough (Va +/+/-- glaucoma can have an APD with good 20/400) central acuity.

3 Identifying & Recording: Exam Clinical Pearls Physiological Anisocoria

„ Ø PERRLA „ BIO > Transilluminator > Penlight „ Neutral Density Filters „ Fat Scan

Physiological Anisocoria Physiologic Anisocoria

„ Anisocoria of < 1mm (to 2mm) „ 20% of the US Population has Simple or Physiological Anisocoria. „ The degree of anisocoria can vary from day to day and even switch sides. „ Unequal supranuclear inhibition in EW nucleus. Fairly consistent across light levels

Which is the Abnormal Pupil? DDX of Anisocoria

„ The pupil that reacts sluggishly to light „ Physiological „ Pharmacological „ Adies Tonic „ AngleAngle--ClosureClosure „ Third N. Palsy „ Trauma „ If Aniso > in Bright => Larger Pupil

„ Parasympathetic Denervation „ Horner’s „ Congenital Malformation / „ If Aniso > in Dim => Smaller Pupil „ Iritis Coloboma „ Abnormal Sympathetic Innervation „ ArgyllArgyll--RobertsonRobertson „ BEPM (Benign Episodic Pupillary Mydriasis

4 Anisocoria: Case History Anisocoria: Case History

„ Temporal Aspects? „ Diplopia? „ Eye Pain? „ Hx of Trauma? „ Decreased VA? „ Drops or Ung’s? „ Arm, Chest, Head, „ Current Medications or Neck Pain? (including OTC’s)? „ Nuchal Rigidity? „ STD’s, Shingles, MS, „ Hx of Stroke, Thyroid Disease, Cancer, or Surgery Diabetes? „ Alcohol Usage?

Anisocoria: Exam Techniques Anisocoria: Exam Techniques

„ VA’s „ Pupillary „ External Assessment: „ Ptosis „ Iris Color „ Anyhdrosis „ Pupil Size(s) & Shape „ Reactivity „ EOM’s „ Dilation Lag „ Color VA, Red „ Near Response Desaturation „ Vermiform Changes „ SLE & Tonometry „ VF Testing & DFE

Anisocoria: Need to Rule-Rule-out!out! Pharmacological Anisocoria

„ Larger Pupil is ABN „ Smaller is ABN „ Adie’s Tonic Pupil „ Horner’s Syndrome „ Compressive III N. „ ArgyllArgyll--RobertsonRobertson „ Pharmacological „ Pharmacological

5 Pharmacology Pharmacology

„ Topical drugs ( Visine ) „ Flea and tick sprays / „ Permethrin: found in „ Systemic drugs. Heroin , morphine , codeine lead to collars / powders some sprays. Has miosis. Dramamine , cocaine , levodopa , and sympathetic effects antihistamines lead to mydriasis. Belladona and (dilation, normal near jimson viiision) „ Angel’s Trumpet (Datura) „ Some cause mydriasis, some cause miosis! „ Anticholinesterase „ Preparation H!!!!!!! (2.5% phenyl) products found in „ Scopolomine motion sickness patches collars, powders, and „ Flea / tick control products foggers: heightened „ 1% pilocarpine test. Will constrict a compressive or parasympathetic effect tonic pupil but not a pharmacological one (miosis, accom. spasm)

Adie’s Tonic Pupil Adie’s Tonic Pupil

„ Stats „ Key Findings „ Females 3:1 „ Dilated pupil with poor to absent direct „ Age: 20-20-4040 response. „ 80% Unilateral „ Tonic near responses Initially „ Reduced Accom „ Becomes bilateral at Amps rate of 1-1-4%4% / year „ Look for segmental „ Etiology palsy of Iris

„ Idiopathic vs. Viral sphincter muscle

Adie’s Tonic Pupil

„ Normal Room Illumination

„ Poor Direct Response „ Fair to Good Concensual

„ (+) Near Response After Prolonged Effort

6 Segmental Palsy Video

Adie’s Tonic Pupil: Additional Testing Adie’s tonic pupil (OD)

„ Dilute (0.125%) Pilocarpine „ Denervation Supersensitivity „ Parasympathetic defect occurs AFTER the fibers leave the Ciliary Ganglion. „ Exaggerated pupillary constriction in the Tonic pupil with little to no constriction of normal pupil. „ Diminshed Deep Tendon Reflexes = „ HolmesHolmes--AdiesAdies Syndrome

Tonic Pupil with & w/o Pilo 0.12% Adies Clinical Pearls

„ With a higher concentration of 1% pilocarpine,pilocarpine, even third-third-nervenerve palsy related pupil will constrict. Pharmdilation likely will not. „ Most cases of the tonic pupil are idiopathic or caused by trauma. „ An acute tonic pupil in patients over 60 years of age warrants an erythrocyte sedimentation rate to rule out giant cell arteritis.arteritis. „ Syphilis needs to be worked up if a patient is male, and has bilateral tonic pupils. „ The tonic pupil is distinguished from other causes of lightlight--nearnear dissociation by the presents of TONIC near response. „ Pharmacological testing, 0.125% pilocarpineor 2.5% methacholine causes denervation supersensitivity. supersensitivity. Image from http://www.atlasophthalmology.com/atlas/photo.jsf?node=5831&locale=en

7 Isolated Third N. Palsy w/ Isolated Third N. Palsy w/ Pupil Involvment Pupil Involvement

„ Sudden Onset Unilateral Ptosiswith Eye or Head Pain „ Acuity is Typically Unaffected unless damage is in Superior Orbital Fissure „ Eye is in non-non-comitantcomitant exotropic & hypotropic position (“down & out”)

Isolated Third N. Palsy 3rd N w/ Pupil Involvement OS

8 Isolated Third N. Palsy w/ Pupil Involvement Pupil sparing / Pupil involving

„ Posterior Communicating Artery Aneurysm (Most Common) „ Rule of thumb : Pupil sparing third nerve „ Tumor or Trauma palsies tend to be ischemic while those „ HZO involving the pupil tend to be due to „ Leukemia aneurysms or tumors „ Uncal Herniation Syndrome „ Not a firm rule „ Space Occupying Lesion „ Pupil sparing may become pupil involving so „ Subdural Hematoma follow very closely „ Pituitary Apoplexy „ Ischemic Vascular Disease (Rare)

Pupil involving vs. pupil Pupil involving vs. pupil sparing sparing

Third Nerve Management Third Nerve Management

„ Immediate Gad enhanced MRI / MRA if „ Patient education and reassurance a any question of aneurysmal must involvement. Patient mayyp complain of a „ Diplopia relief with patching severe headache and will often have „ Most ischemic palsies resolve over other neurological signs several months „ If patient is diabetic or hypertensive and the pupil is not involved they can be followed closely without imaging studies

9 Isolated Third N. Palsy w/ Pupil Involvement Horner’s Syndrome

„ Management „ Hospital Neurosurgical Consult ASAP „ CT/MRI/MRA „ Lumbar Puncture „ Cerebral Angiography

Anatomy of the Sympathetic Horner’s Syndrome: Pathway to the Eye Clinical Features

A. Moderate Ptosis (2(2--3mm)3mm) due to paralysis of Muller’s muscle B. “Upside Down Ptosis” - Mild elevation of the lower lid due to paralysis of the smooth muscle attached to the inferior tarsal plate. C. Apparent Enophthalmos due to A & B above D. + Dilation Lag (classic finding) E. Decreased IOP on affected side

Horner’s Syndrome: Dilation Lag Clinical Features

F. Miosis, more noticeable in dim illumination. Note: Pupil rxns to light and near are normal. G. Anhydrosis on Ipsilateral side of face if lesion is below the Superior Cervical Ganglion => Not a 3rd order neuron. H. Increase in Amplitude of Accommodation due to unopposed action of the parasympathetic.

10 Horner’s pupil (OS) Horner’s

„ Miosis with normal reaction to light „ Ptosis and upside down ptosis ( loss of muscle tone ) „ Heterochromia if congenital and anhydrosis if the lesion is below the SC ganglion but before the carotid bifurcation „ Hypotony „ Can occasionally get partial involvement with ptosis only (no miosis)

Horner’s Syndrome: Horner’s: Clinical Features…Lastly Localization of Lesion

„ 4% Cocaine „ + Test => Anisocoria will increase „ Hydroxyamphetamine (Paradrine 1%) „ Preganglionic lesion => YES dilation „ Postganglionic lesion => No dilation „ If suspect pre-pre-ganglionicganglionic lesion => Chest CT or XX--ray.ray.

Most Common Causes of Horner’s Horner’s Syndrome

„ Testing ; 4% cocaine will dilate a normal pupil by blocking the re-uptake of epinephrine but will not dilate the Horner’s pupil. Shelf life of only six months if preserved and cost of $90 „ More practical: 1% Iopidine will dilate a Horner’s pupil after 30-45 minutes but will not dilate a normal pupil. 0.5% works also „ 1% hydroxyamphetamine will dilate a first or second order Horner’s but not a third by releasing NE from postganglionic synapses. Must wait one hour to check and need 72 hour washout if cocaine was used „ Ptosis only patients will get lid elevation with Naphazoline. Little pupillary mydriasis.

11 Horner’s Causes Wallenberg’s syndrome

„ First order : Neoplasms , Wallenberg’s „ Stroke of vertebral „ Difficulty swallowing syndrome , trauma , vertebral - basilar or posterior inferior „ Hoarseness insufficiency cerebellar artery in „ Dizziness „ Second order : Pancoast or thyroid tumor , the brai nst em „ Nausea neck trauma or surgery „ Gait disturbance „ Third order : Cluster headaches , cavernous sinus lesion , dissecting carotid aneurysm „ Nystagmus „ Uncontrollable „ Testing: MRI , MRA , and chest X-ray hiccups

Raeder’s syndrome ArgyllArgyll--RobertsonRobertson Pupil „ Horner’s with pain in the distribution area of V1. Caused by a neoplasm compressing the trigeminal nerve. Differential for cluster headaches.

ArgyllArgyll--RobertsonRobertson Pupil: Argyll - Robertson Clinical Features „ Bilateral, asymmetrically miotic pupils which are „ Pupils are small and frequently irregular irregular „ Key Finding: LND Pupil „ Poor dilation with poor response to light „ Bilateral Asymmetric Pupil Involvement but brisk near „ VA’s are typically NORMAL response „ Poor dilation with Mydriatics „ Hallmark of tertiary neurosyphilis.

12 ArgyllArgyll--RobertsonRobertson pupil AR Pupils

ArgyllArgyll--RobertsonRobertson Pupil: WorkWork--upup

„ As this is a Hallmark Sign for Neurosyphilis, need to rule this out, as well as HIV:

„ FTAFTA--Abs,Abs, VDRL „ Neurological workwork--upup „ Consider MRI, Lumbar Puncture

Anisocoria Case Report Anisocoria Case Report

„ 55 yr. Old caucasian female „ Clinical Findings: „ CC: droopy eyelid OD for 1 month, no „ BVA: 20/20 OD, OS other complaints or symptoms . „ Pupils: „ ((--)) APD „ Patient & Family Ocular & Medical Hx – Negative „ Size (light): 2.5mm OD, 3.0mm OS „ Size (dim): 3.0mm OD, 6.5mm OS

„ Medications: Evista, Calcium Sup. „ ((--)) LND „ EOM’s / CT: Normal

13 Anisocoria Case Report Anisocoria Case Report

„ Clinical Findings Continued: „ Clinical Findings „ Lid Eval „ TA: 10/12 „ UL 2mm on cornea OD; IPF 5mm „ SLE: Normal „ UL 1mm above cornea OS; IPF 8mm „ DFE: C/D: 0.2 OD, 0.2 OS (good color) „ LL elevation OD „ Macula & Retina: Normal OU „ Iris Color Equal

Q1: Which of the following tests is least Q1: Which of the following tests is least appropriate to confirm the diagnosis? appropriate to confirm the diagnosis?

1. 44--10%10% Cocaine test 1. 44--10%10% Cocaine test 2. .125% Pilocarpine test 2. .125% Pilocarpine test 3. Paradrine 1% test 3. Paradrine 1% test 4. All of the above 4. All of the above 5. None of the above 5. None of the above

Q2: Which of the following is Q2: Which of the following is the most likely diagnosis? the most likely diagnosis?

1. Congenital Horner’s Syndrome 1. Congenital Horner’s Syndrome 2. Acquired Horner’s Syndrome 2. Acquired Horner’s Syndrome 3. Adie’ ssTonicPupil Tonic Pupil 3. Adie’ ssTonicPupil Tonic Pupil 4. CN III Palsy 4. CN III Palsy 5. ArgyllArgyll--RobertsonRobertson Pupil 5. ArgyllArgyll--RobertsonRobertson Pupil

14 Q3: Which of the following is NOT considered Q3: Which of the following is NOT considered appropriate management for this condition? appropriate management for this condition?

1. Chest XX--RayRay 1. Chest XX--RayRay 2. Brain Imaging 2. Brain Imaging 3. Referral to a Neurospecialist 3. Referral to a Neurospecialist 4. All of the above are appropriate 4. All of the above are appropriate 5. None of the above are appropriate 5. None of the above are appropriate

Q4: Which of the following indicates the Q4: Which of the following indicates the congenital / infantile form of this condition? congenital / infantile form of this condition?

1. Mild Ptosis with excellent levator 1. Mild Ptosis with excellent levator function function 2. Miotic Anisocoria , most apparent in 2. Miotic Anisocoria , most apparent in darkness darkness 3. Lower Lid Elevation 3. Lower Lid Elevation 4. Ipsilateral Anhydrosis 4. Ipsilateral Anhydrosis 5. Heterochromia 5. Heterochromia

Thank You!

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