Anisocoria: Symptoms, Types, Causes and Treatment

Anisocoria, or unequal pupil size, is a subtle sign that can be easily overlooked yet may have significant clinical implications. Sometimes it’s completely harmless, but in other cases, it can signal a serious underlying condition. This article explores the symptoms, types, causes, and treatment of anisocoria, drawing on recent clinical research and real-world case studies.

Symptoms of Anisocoria

Anisocoria often comes to light during a routine eye exam or when someone notices a difference in their pupil sizes while looking in the mirror. However, anisocoria can also be accompanied by other symptoms, and understanding these can be crucial for timely and accurate diagnosis.

Symptom	Associated Features	Severity/Duration	Source(s)
Unequal pupils	May be constant or episodic	Usually transient or persistent	1, 6
Blurred vision	Often in affected eye	Temporary	1, 5
Photophobia	Sensitivity to light	Temporary	5
Headache	Unilateral, rare	Transient	1
No symptoms	Detected incidentally	Persistent or transient	4, 6

Table 1: Key Symptoms of Anisocoria

Understanding the Symptoms

Unequal Pupils

The defining symptom of anisocoria is a visible difference in the diameter of the pupils. This can be constant or fluctuate over time. In many cases, individuals are unaware of this difference unless pointed out by someone else or discovered during a medical exam 1, 6.

Visual Disturbances

Blurred vision is a common symptom, particularly when anisocoria is sudden in onset or caused by exposure to certain medications or toxins. Photophobia, or increased sensitivity to light, can also occur, especially when the affected pupil is unable to constrict properly 1, 5.

Headache and Other Associated Signs

Occasionally, anisocoria may be accompanied by a unilateral headache, typically on the same side as the larger pupil. However, this is relatively rare and more likely to be reported in acute or pharmacologic cases 1.

Asymptomatic Cases

Not all individuals with anisocoria experience symptoms. In many cases, especially physiological anisocoria, the difference in pupil size is small and not associated with any other complaints 4, 6.

Types of Anisocoria

Anisocoria can be categorized in several ways, depending on its cause, duration, and clinical context. Understanding these types helps clinicians distinguish benign from potentially life-threatening cases.

Type	Characteristics	Typical Course	Source(s)
Physiological	Mild, stable size difference	Persistent, harmless	4, 6
Pharmacologic	Linked to drug or toxin exposure	Transient, resolves	1, 2, 5, 6, 7
Pathological	Due to nerve or brain disorders	Variable, may worsen	3, 4, 7, 8
Episodic/Benign	Intermittent, no clear cause	Resolves spontaneously	6

Table 2: Types of Anisocoria

Classifying Anisocoria

Physiological Anisocoria

This common type affects up to 20% of the population and is considered a normal variant. The difference in pupil size is typically less than 1 mm and remains consistent under different lighting conditions. Importantly, there are no associated neurological or ocular symptoms 4, 6.

Pharmacologic Anisocoria

Exposure to certain medications—either systemic or topical—can cause the pupils to dilate unevenly. Examples include accidental eye exposure to anticholinergic wipes (e.g., glycopyrronium) or nebulized bronchodilators like ipratropium bromide 1, 2, 5, 6. This type is usually transient and resolves once the drug’s effects wear off.

Pathological Anisocoria

This form results from damage to the nerves controlling the pupil (e.g., third nerve palsy, Horner syndrome) or from intracranial processes such as tumors, strokes, or infections. Pathological anisocoria may progress and is often accompanied by other neurological symptoms 3, 4, 7, 8.

Episodic or Benign Anisocoria

Some individuals, especially children, may experience episodes of anisocoria that occur unpredictably and resolve without intervention. These cases are often termed "benign episodic unilateral mydriasis" and are not associated with any underlying disease 6.

Causes of Anisocoria

Anisocoria has a broad differential diagnosis, ranging from harmless to potentially life-threatening. Accurate identification of the underlying cause is essential for appropriate management.

Cause	Mechanism/Pathway	Typical Presentation	Source(s)
Medications	Anticholinergics, SSRIs, others	Acute, transient	1, 2, 5, 6, 7
Neurological	Nerve palsy, stroke, tumors	Gradual or acute	3, 4, 7, 8
Systemic Disease	Diabetes, MS, infections	Variable	4
Psychological	Emotional/psychogenic factors	Rare, uncertain	4
Trauma	Ocular or brain injury	Acute	4
Idiopathic	No identifiable cause	Often benign	6

Table 3: Major Causes of Anisocoria

Exploring the Origins

Drug-Induced (Pharmacologic) Anisocoria

• Anticholinergic Agents: Products like glycopyrronium wipes, used for excessive sweating, can cause pharmacologic mydriasis if they come into contact with the eye. Several pediatric and adult cases have been reported, with symptoms resolving after discontinuation 1, 5.
• Nebulized Medications: Ipratropium bromide, a bronchodilator, can cause unilateral pupil dilation if the aerosol leaks into one eye—especially when using ill-fitting masks during asthma treatments 2.
• SSRIs and Other Drugs: Although rare, SSRIs have been linked to anisocoria, likely due to their effect on serotonin receptors in the eye, resulting in muscle relaxation and pupil dilation 7.

Neurological Disorders

• Third Nerve Palsy: Damage to the oculomotor nerve can prevent the affected pupil from constricting, leading to anisocoria. This may result from aneurysms, tumors, or trauma 3, 4, 7.
• Horner Syndrome: Disruption of the sympathetic pathway causes a smaller pupil (miosis) on the affected side, often accompanied by ptosis and loss of sweating 3, 4, 7.
• Stroke and Intracranial Lesions: While isolated anisocoria is rarely the sole sign of acute stroke, it is more significant when occurring alongside other neurological deficits—particularly in posterior circulation strokes 8.

Systemic and Other Medical Conditions

Anisocoria can be associated with a variety of systemic diseases, including diabetes, multiple sclerosis, encephalitis, tumors, thyroid dysfunction, and various forms of neural dysfunction 4. Sometimes, infections like tuberculosis meningitis or even mumps are implicated 4.

Psychological and Idiopathic Factors

Emotional states or psychological conditions have occasionally been linked to anisocoria, but the evidence for these associations is limited and often debated 4. Many cases, particularly in children, remain idiopathic—meaning no clear cause can be identified 6.

Treatment of Anisocoria

The management of anisocoria depends entirely on its underlying cause. While many cases are benign and self-limiting, others require targeted intervention.

Treatment Approach	Indication	Outcome/Prognosis	Source(s)
Observation	Physiological/benign	Resolution or persistent, harmless	1, 4, 6
Remove offending drug	Pharmacologic	Rapid resolution	1, 2, 5, 6
Treat underlying disease	Neurological/systemic	Variable, depends on cause	3, 4, 7, 8
Diagnostic testing	Unclear/acute cases	Guides management	2, 3, 6

Table 4: Treatment Strategies for Anisocoria

Tailoring Management

Observation and Reassurance

Physiological and benign episodic anisocoria require no treatment. Patient education and reassurance are vital, as awareness of the benign nature can prevent unnecessary anxiety and medical testing 1, 4, 6.

Removing the Trigger

In pharmacologic anisocoria, identifying and discontinuing the offending agent leads to rapid improvement. For instance, switching from anticholinergic wipes or preventing nebulizer leakage into the eye can resolve symptoms within hours to days 1, 2, 5, 6.

Addressing Underlying Pathology

If anisocoria is due to a neurological or systemic condition, treatment must target the root cause. This may include managing diabetes, treating infections, or urgent interventions for strokes, tumors, or nerve palsies 3, 4, 7, 8. Isolated anisocoria rarely warrants acute stroke treatment unless accompanied by other neurological deficits 8.

Diagnostic Tools

Pharmacological testing—such as the pilocarpine test—can help differentiate between pharmacologic and neurological causes, guiding further management. A thorough medication and exposure history is equally important 2, 3, 6.

When to Seek Immediate Care

• Sudden onset of anisocoria with other neurological symptoms (e.g., double vision, weakness, severe headache) warrants emergency evaluation.
• Anisocoria that develops after head trauma or in association with stroke symptoms also needs urgent medical attention.

Conclusion

Anisocoria is a frequent and often benign finding, but it can occasionally signal a serious underlying disorder. Understanding its symptoms, types, causes, and treatments is crucial for both clinicians and patients. Key takeaways include:

• Anisocoria is defined as unequal pupil size; it may be harmless or indicate serious disease.
• Symptoms range from visual changes to headaches, but many cases are asymptomatic.
• Types include physiological, pharmacologic, pathological, and episodic forms.
• Causes are diverse, from medications and neurological disorders to systemic or idiopathic origins.
• Treatment depends on the cause, with many cases requiring only observation or discontinuation of a triggering agent.
• Pharmacological testing and careful history-taking are essential for accurate diagnosis.
• Immediate evaluation is needed if anisocoria is sudden and accompanied by other neurological signs.

By staying informed, both patients and healthcare providers can distinguish between harmless and worrisome forms of anisocoria, ensuring prompt and appropriate care when needed.