What Causes Anisocoria?

Patient Presentation
A 14-year-old male came to clinic after a history of hitting his head on a goal post while playing soccer 6 days before. He had “seen stars” initially but said he felt relatively well for the rest of practice. He had a soccer game the following day where he said he felt “slow and tired.” He had a dull generalized headache since the incident that waxed and waned from a dull headache to moderate (6/10 rating). The headache was worse with increases in sound and light. Sleep was okay and he was not having problems necessarily listening at school or doing his homework but was more tired. He told his parents about the symptoms on day 5 and the parents made this appointment. The past medical history showed no head injuries or neurological problems.

The pertinent physical exam showed normal vital signs with growth parameters in the 50-90% for age. His neurological examination was normal including balance and gait. His mental status examination was normal. His sport concussion assessment tool had 8 of 22 symptoms with most in the mild range. His parent endorsed 5 symptoms.

The diagnosis of a concussion was made. The patient was asked to do brain rest for 1 week, given head injury instructions and asked to return to clinic in one week. The patient’s clinical course was that the following week he saw a different clinician and showed that he had been going to school still but had not been participating in athletics. He had continued symptoms but were slightly improved symptoms with only 6 on the sports assessment tool but headache and tiredness were his main complaints. He denied any vision problems. On physical examination he had a right pupil that was 3-4 mm and a left pupil that was 2-3 mm in size. Both were round, reactive to light and accommodation. All extra ocular movements were intact. There was no increased lacrimation and his disc margins were sharp. He said he was still a little tender where he had hit the pole with his head but a detailed head and neck and neurological examination revealed no focal findings.

The diagnosis of concussions with a new notation of anisocoria was made. His mother said she couldn’t really remember him having different sized pupils but that she had one herself which the clinician noted to be about 1 mm different in size. As the patient had no neurological findings and his overall symptoms were improving, it was decided to watch him and the family would call with any vision or neurological changes. They decided together that he could continue going to school but no atheletics. The patient’s clinical course showed that he still had a similar physical examination and he was slowly improving with only 3 symptoms noted on repeated sport concussion assessment tool but still with some headaches. Followup after one more week showed the patient still to have anisocoria but no symptoms.

Anisocoria is a common physical finding caused by the mechanical imbalance of the iris dilator (sympathetic innervation causing dilation) and sphincter muscles (parasympathetic innervation causes miosis).

Which pupil is abnormal is important to determine. “Anisocoria greater in the light signifies an abnormal large pupil, whereas anisocoria in the dark indicates an abnormal small pupil.” The pupillary size should be noted along with any changes with accommodation, extra ocular movements and lighting. The time it takes to revert to the baseline pupillary size can also be helpful. Any ptosis, lacrimation and pain should be noted. Evidence of papilledema should be looked for. Additionally, a thorough head and neck examination and neurological examination are important to look for additional diagnostic clues. While a generalist may not be able to interpret all of these signs and symptoms, gathering this information and discussion with an ophthalmologist and/or neurologist can be helpful.

Physiologic anisocoria is common with approximately 15-30% of the normal population having this physical finding. “Physiologic anisocoria should be longstanding, neurologically isolated, less than 1 mm in size discrepancy, and stable in light and dark conditions.” Old photographs may be helpful and reassuring.

Evaluation for anisocoria may include pharmacologic testing, and imaging of the head and/or neck and potentially other body areas.

Learning Point
The differential diagnosis of anisocoria includes:

  • Physiologic
  • Third nerve palsy
    • Mid-range dilation not reactive to light or convergence
    • Can be caused by mass/compressive lesions or other reasons the nerve is irritated
    • Aneurysms as a cause are uncommon in children and may cause pain
  • Tonic or Adie pupil
    • Large pupil in young women that slowly dilates after accommodation
    • Usually unilateral but can be bilateral
  • Horner syndrome
    • Classic triad of miosis (unilateral), ptosis and anhidrosis
    • Causes of Horner syndrome includes various benign and malignant tumors, syndromes, vascular abnormalities, trauma and deep infections of the neck
    • Often congenital including birth trauma as a cause
  • Drugs
    • Usually due to accidental exposure including:
      • Dilators: scopolamine, ipratropium, glycopyrrolate, nasal vasoconstrictors and plants such as blue nightshade, Jimson weed and Angel’s trumpet
      • Constrictors: clonidine, opioids, organophosphates, pilocarpine and prostaglandin
  • Trigeminal autonomic cephalgias
    • Headaches with unilateral sympathetic problems including rhinorrhea and increased lacrimation. Horner syndrome with ptosis can be seen
    • Autoimmune autonomic ganglionopathy
      • Autoantibodies target autonomic ganglia and anisocoria can be seen
      • Other dysautonomia syndrome often occur

Questions for Further Discussion
1. What is the general guidance for return to learning after head injury? A review can be found here
2. How long do concussive symptoms last? A review can be found here
3. What causes ptosis? A review can be found here
4. How common is ocular trauma? A review can be found here
5. List of the autonomic nervous system disorders?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Eye Diseases and Autonomic Nervous System Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Patel R, Davis C, Sivaswamy L. Anisocoria–not always cause for alarm. J Pediatr. 2014;164(6):1497. doi:10.1016/j.jpeds.2014.02.004

Gross JR, McClelland CM, Lee MS. An approach to anisocoria. Curr Opin Ophthalmol. 2016;27(6):486-492. doi:10.1097/ICU.0000000000000316

Harer K, Alverson B. Eye-opening Etiologies. Hosp Pediatr. 2018;8(5):300-301. doi:10.1542/hpeds.2017-0204

McEachern W, Walz A, Dantuluri K, Dulek D, Betters K. Case 3: Anisocoria in a 5-year old Girl. Pediatr Rev. 2019;40(7):366-368. doi:10.1542/pir.2018-0132

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa