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The Ultimate Guide to Pupil Abnormalities

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Here is everything you need to know about abnormalities affecting the pupil!

The Ultimate Guide to Pupil Abnormalities

In optometry school, our professors often stress how important close observation of a patient’s pupils can be in assessing his or her ocular and systemic health.
However, in every day practice, this facet of the exam can be easily overlooked, particularly if technicians are checking instead of doctors. In an effort to remind us of the importance of this exam element, this guide will review how to discern between different presentations of anisocoria, as well as touch on some of the other causes of abnormal pupil findings.

ANISOCORIA: unequal pupil sizes

When a patient presents with unequal pupils, it is integral to determine which pupil has the problem.
In order to do this, the clinician should check the pupil size in both dark and bright conditions.
Anisocoria that is greater in dim lighting indicates that the smaller pupil is unable to dilate to the degree of the larger pupil, and is therefore, the problem.
Two conditions to keep in mind that can lead to inability to dilate normally/miotic pupils are:

1. Horner’s syndrome

  • Interruption in the sympathetic nervous system pathway which controls mydriasis in normal circumstances
  • Can be first, second, or third order depending upon which area of the pathway is affected
    • First order refers to the part of the pathway from the hypothalamus to C8-T1
      • Possible etiology: stroke
    • Second order refers to C8-T1 to the superior cervical ganglion
      • Possible etiology: Pancoast tumor
    • Third order is anything beyond the superior cervical ganglion to the pupil dilators and lid
      • Possible etiology: problem at the internal carotid; cavernous sinus problem
  • Typically presents with anisocoria (worse in dim lighting) and mild ptosis; the smaller or miotic pupil is the affected pupil
  • Pharmacologic testing can be used to confirm Horner’s and indicate which part of the pathway has been affected
    • Confirming Horner’s
      • 4-10% cocaine drops
        • A Horner’s pupil WILL NOT dilate after instillation (normal pupil will)
      • 1% or 0.5% apraclonidine
        • A Horner’s pupil WILL dilate MORE than the normal pupil, reversing the anisocoria
    • Determining which order is affected
      • Hydroxyamphetamine
        • To be used only after confirmation testing has been performed
        • Will dilate the Horner’s pupil as long as the third order pathway is intact

Remember the phrase: FAIL SAFE

If hydroxyamphetamine fails to dilate your patient, they are likely safe from 1st and 2nd order problems, such as a Pancoast tumor or stroke. However, clinicians should remember that an internal carotid problem (aneurysm/dissection) can cause a third order Horner’s Syndrome.

2. Pharmacologic

  • Most commonly, the patient has been exposed to pilocarpine
  • Opioids/opiates can cause miosis, typically bilaterally
  • Pupil will not dilate normally with instillation of any medication
  • Thorough history is key
As opposed to small pupil problems, anisocoria in which the larger pupil is affected will be most exaggerated in bright lighting. Third nerve palsy, Adie’s Tonic Pupil, and pharmacologic dilation are three common causes of “big pupil” problems.

1. Third Nerve Palsy

  • Full presentation includes mydriasis, ptosis, and restricted EOM’s often resulting in a “down and out” appearance of the affected eye
    • Can present with mild signs, and pupil involvement may not be seen in early or ischemic cases
  • Pupil involvement suggests possible aneurysm or compressive lesion
  • Patients who present with ptosis and EOM restriction, but no pupil involvement, are likely suffering from ischemia affecting the 3rd cranial nerve (most commonly due to diabetes)
  • All patients presenting with a CN3 palsy should be imaged to evaluate for impending aneurysm regardless of pupil involvement, and clinicians should re-evaluate a patient’s pupils often during the early presentation of the condition to determine if the pupil is becoming mydriatic
  • Ischemic cases typically resolve in 3-6 mo; compressive cases do not resolve until the underlying systemic cause is addressed

2. Adie’s Tonic Pupil

  • Mydriatic pupil will not constrict with light, will constrict when in near gaze (light-near dissociation)
  • Will take longer than a normal pupil to release the miosis reached in near gaze after looking away from the near target
  • Pupil will constrict with instillation of weak (0.1%) pilocarpine, which will minimally or not affect a normal pupil
  • Caused by damage to the postganglionic parasympathetic pupil pathway
  • More common in females than males and usually unilateral
  • Main cause is unknown; Herpes-zoster, varicella, giant cell arteritis, and orbital trauma can cause Adie’s in rare cases

3. Pharmacologic

  • As with miotic pupils, thorough history is key
  • Will present with one or both pupils fixed and dilated in early stages, may be slightly reactive to light as agent wears off
  • Beyond a patient’s abuse of dilation drops, common causative drugs that can result in mydriasis include scopolamine patches for motion sickness (may present with dilation only on the side to which the patch was applied), cold medications/decongestants, marijuana, and stimulants (cocaine, meth, etc)

REMEMBER: Physiologic anisocoria is not uncommon. However, unlike anisocoria caused by an underlying condition, there will be minimal difference in amount of anisocoria in both light and dim conditions.

Outside of anisocoria, pupil shape and reactivity are also important indicators of a patient’s health and history.
Irregularities in pupil shape are most frequently the result of trauma that has affected the iris, but may also develop secondary to long-standing synechia or surgical complications.


The most important abnormal reactivity finding is the afferent pupillary defect (APD).

As a review, this means that the affected pupil has an interruption in the transmission pathway that relays information from the retina/optic nerve to the brain. It is important to remind staff that all APDs should be documented and that they are still able to check for an APD even if the patient has one pupil fixed.
If an APD is observed in a patient without remarkable explanatory history (end-stage glaucoma, hx of retinal detachment, etc), the clinician should be prepared to perform a thorough evaluation of the retina and optic nerve as well as any additional testing needed to discern the cause of the defect.
Pupils can be one of the most informative elements of an ophthalmic examination, and with close attention and thorough staff education, clinicians can diagnose many conditions, some of which may help catch potentially life-threatening conditions.
To steal a line from Grey’s Anatomy,

“It’s a great day to save lives.”

Happy pupil checking, everyone!

  1. Eggenberger, Eric R. “Anisocoria.”
  2. “Adie Tonic Pupil.” American Academy of Ophthalmology.
  3. Canellos, Evan C. “My Patient has an RAPD! Now What?”
Patricia Fulmer, OD, FAAO
About Patricia Fulmer, OD, FAAO

Dr. Fulmer is the sole owner of Legacy Vision Center, a cold start, medically focused practice in Huntsville, AL, which launched at the end of 2020. A graduate of the UAB School of Optometry, she completed an ocular disease and primary care residency at the Thomas E. Creek VA Medical Center before returning to Alabama to serve as the Center Director and consultative optometrist for a referral-based, tertiary care facility and then as an associate at a multi-doctor family practice. Her clinical interests include disease management, particularly glaucoma, uveitis, dry eye, and neurology-related cases, as well as educating students and colleagues through lecturing and writing. She is an active member in the American Academy of Optometry and American Optometric Association and currently serves her profession as a member of the Board of Directors of the Alabama Optometric Association and as President of the North Alabama Optometric Association. In her free time, Dr. Fulmer enjoys spending time with her husband and family, spoiling their fur-babies, traveling, attending concerts, and exploring the outdoors while kayaking and hiking. She also loves giving back through volunteering, including serving on the Board for HEALS, Inc, an organization that focuses on providing healthcare to local in-need youth.

Patricia Fulmer, OD, FAAO
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