1 Introduction
Prone positioning is used for managing severe respiratory failure, especially in patients with acute respiratory distress syndrome (ARDS), by enhancing ventilation‐perfusion matching and air distribution. Despite its survival benefits, the position places patients at risk for rare but severe complications [
1]. Among these, the development of anisocoria (unequal pupil size) often raises immediate concern for neurological emergencies like intracranial hemorrhage, stroke, or uncal herniation.
However, emerging evidence suggests that anisocoria in the intensive care unit (ICU) may also arise from benign, transient mechanisms related specifically to prone positioning. The actual prevalence of this phenomenon remains undetermined, as pupillary changes may be underreported or obscured by positioning devices. Understanding these mechanisms is essential, as it helps clinicians recognize the transient nature of this condition and guides appropriate clinical decision‐making.
2 Mechanism 1: Angle‐Closure Glaucoma
In one reported case, a 74‐year‐old man with COVID‐19–related ARDS developed unilateral pupillary dilation while sedated in the prone position. Baseline pupils were equal and reactive (3 mm each) before proning. Dilation of the left pupil to 6 mm developed approximately 18 h into the proning session. At this time, no focal neurological deficits were observed; brainstem reflexes remained intact, and motor response was appropriate for the sedation level (Glasgow Coma Scale [GCS] remained stable). No new motor or sensory deficits were identified, and brainstem reflexes (including pupillary and corneal reflexes) remained intact. Neuroimaging ruled out intracranial pathology, and ophthalmologic evaluation diagnosed subacute angle‐closure glaucoma. This occurs because prone positioning causes a gravity‐dependent anterior shift of the lens‐iris diaphragm. In anatomically predisposed individuals, especially those with hyperopia (farsightedness) or a family history of glaucoma, the ocular anatomy favors anterior displacement of the lens‐iris diaphragm during prone positioning. This movement precipitates the pupillary block, where aqueous humor is trapped in the posterior chamber of the eye, bowing the peripheral iris forward and obstructing the trabecular meshwork. This leads to an acute rise in intraocular pressure (IOP), which is further exacerbated by venous congestion and impaired orbital venous outflow commonly seen in prone positioning. Unlike positional causes, this mechanism required targeted glaucoma therapy, with resolution occurring over several days [
2]. No signs of stroke or brainstem involvement were noted, supporting a benign versus neurological emergency etiology.
3 Mechanism 2: Horner Syndrome
In another case, a second ARDS patient developed miosis and ptosis features of Horner syndrome which resolved spontaneously upon returning the patient to a supine position [
3]. Baseline examination indicated symmetric 4 mm pupils. Miosis and 2 mm of ptosis in the right eye developed 8 h after initial prone positioning. As in the first case, there were no new focal neurological deficits, no motor or sensory abnormalities, and brainstem reflexes were preserved, and the GCS was unchanged from the patient's clinical baseline. Complete resolution occurred approximately 45 min after returning to the supine position. The mechanism behind positional Horner syndrome depends on the site of disruption in the sympathetic pathway. While central (first‐order) lesions are typically related to brainstem pathology, preganglionic (second‐order) fibers are vulnerable to compression as they traverse the lung apex and neck—areas highly susceptible to pressure changes during prone positioning. Postganglionic (third‐order) fibers, which ascend the internal carotid artery, may also be affected by extreme neck rotation or severe local venous congestion. Although both cases presented similarly, their timing of resolution differed: the first one required specific glaucoma therapy, while the second resolved immediately with repositioning. In persistent cases, standard diagnostic protocols often involve apraclonidine testing to confirm sympathetic denervation in Horner syndrome. The absence of accompanying stroke signs or other brainstem findings differentiates this clearly from a neurological emergency. These differences highlight the underlying pathophysiology: angle‐closure glaucoma results from mechanical obstruction of aqueous humor outflow and requires targeted therapy, whereas positional Horner syndrome is caused by transient sympathetic pathway compression and typically resolves with simple repositioning.
Due to the pupillary abnormality, both patients urgently needed neurological evaluation; however, no life‐threatening cause was found. Ocular and positional factors can therefore mimic more serious conditions, such as brain herniation. Recognizing these patterns enables clinicians to stay vigilant and avoid nonessential interventions in patients who do not display additional neurological signs or clinical deterioration. Importantly, the transient nature of these findings reflects reversible mechanical compression and venous congestion, differentiating them from life‐threatening causes such as uncal herniation, where anisocoria results from irreversible third cranial nerve compression.
Several factors can cause unilateral pupillary dilation during prone positioning [
4,
5]. A primary mechanism is orbital compression, which increases IOP and may mechanically affect the iris or cranial nerves [
4]. Proposed mechanisms suggest that extended compression, especially in patients with vascular compromise, leads to significant venous congestion. This increases episcleral venous pressure, which obstructs the drainage of aqueous humor, further elevating IOP [
4,
5]. Prolonged compression may also cause visual deficits, diplopia (double vision), ptosis (drooping eyelid), or anisocoria (unequal pupil size), resulting from transient third cranial nerve involvement rather than structural damage [
5]. Impaired venous return can lead to periocular congestion, which may contribute to jugular vein compression, cerebral venous congestion, or increased intracranial pressure. Rarely, a cerebral venous sinus thrombosis may occur. In mechanically ventilated patients, the sedatives and muscle relaxants they receive can affect pupillary reactivity and hemodynamics. Certain inhaled medications, such as ipratropium bromide, may cause transient anisocoria [
6]. If blood flow to the brain is severely disrupted, it can lead to a stroke or dangerous pressure that causes the brain to shift, which are emergencies that require immediate imaging and treatment.
4 Diagnostic Algorithm for Anisocoria During Prone Positioning
The occurrence of anisocoria in patients undergoing prone positioning may raise concern for serious neurological pathology. However, positional factors, ocular conditions, and pharmacologic agents may also produce transient anisocoria. To assist clinicians in distinguishing benign causes from life‐threatening conditions, a simplified diagnostic algorithm for evaluating anisocoria in patients undergoing prone positioning is shown in Figure 1. The algorithm incorporates key clinical features, including timing of onset relative to proning, associated neurological or ocular signs, hemodynamic stability, pupillary characteristics, and response to repositioning. It follows a stepwise approach beginning with rapid neurological assessment, followed by evaluation of positional factors and ocular causes, and finally determination of the need for urgent neuroimaging based on red flag signs. Benign (positional) anisocoria should be assumed when anisocoria appears after prone positioning, develops in the absence of newly emerging focal neurological deficits, and subsides with repositioning or targeted ocular therapy. Further reassuring indicators include stable hemodynamics, preserved brainstem reflexes, and unchanged GCS. Urgent neuroimaging is recommended when anisocoria presents with clinical signs suggestive of a neurological emergency. These signs include: new focal neurological deficits, altered level of consciousness, loss of brainstem reflexes, hemodynamic instability, lack of improvement after repositioning, and progressive/worsening pupillary dilation.
5 Pupillary Monitoring in Patients Undergoing Prone Positioning
Pupillary examination remains an important component of neurological monitoring in critically ill patients; however, assessment may be challenging in individuals placed in the prone position because the eyes may be partially obscured by positioning devices. Routine ocular and pupillary assessment forms part of neurological monitoring and eye care in critically ill patients [
7].
To facilitate monitoring, clinicians should ensure appropriate head positioning to minimize orbital compression and allow periodic visualization of the eyes. Baseline pupillary size and reactivity should be recorded before proning and reassessed during routine neurological examinations. Automated pupillometry may provide an objective method for measuring pupil size and reactivity in sedated or mechanically ventilated patients in certain settings [
7]. Pupillary checks should be performed at scheduled intervals following a structured protocol, this includes documentation of pupil size, symmetry, and reactivity to light. Both direct and consensual responses should be assessed whenever possible. Measures should be taken to minimize excessive manipulation of the eyelids or globe during examination. Preventative interventions during prone positioning include: maintaining the head in a neutral position to reduce vascular and neural compression, avoiding direct orbital pressure by using appropriate positioning devices, to prevent external compression by applying protective eye padding, and regular revaluation of the head and eye alignment during prolonged proning.
6 Clinical Take‐Home Points
• Anisocoria developing after prone positioning in the absence of new neurological deficits is often benign and positional.
• Immediate neuroimaging is warranted only when accompanied by red flag signs such as altered consciousness, focal deficits, or loss of brainstem reflexes.
• Repositioning should be the first diagnostic and therapeutic step in suspected positional anisocoria.
• Preventive strategies, including neutral head positioning, avoidance of orbital compression, and protective eye padding, are essential.
In conclusion, anisocoria observed during prone positioning represents a critical diagnostic challenge in intensive care. While it may signal life‐threatening neurological pathology, it is frequently due to reversible positional or ocular mechanisms. A structured clinical approach incorporating neurological assessment, positional evaluation, and selective use of neuroimaging is essential to avoid unnecessary interventions. Emphasis on preventive strategies and vigilant monitoring can significantly improve patient safety and reduce avoidable diagnostic burden in critically ill patients.
2026 The Author(s). Eye & ENT Research published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.
PDF
(600KB)
