Transdermal and Powdered Scopolamine-Induced Anisocoria: A Report of Two Cases Open Access

Introduction: In this case report, we present 2 cases of sudden-onset anisocoria caused by accidental exposure to scopolamine in 2 young female patients. Case Presentation: Two patients presented with unilateral anisocoria. One patient experienced unilateral mydriasis accompanied by neurological symptoms from a transdermal scopolamine patch, while the other, exposed to powdered scopolamine, presented with unilateral mydriasis without additional neurological symptoms. Both cases showed gradual resolution of symptoms over several days without intervention. Initially, Adie’s pupil (tonic pupil) was high in the differential diagnosis, but a comprehensive history taking revealed scopolamine exposure as the more likely cause. In the first case, pilocarpine did not result in miosis, while in the second case, pilocarpine initially induced miosis but was followed by a return to mydriasis. Although current literature suggests that mydriasis caused by an anticholinergic substance presents as pupil dilation unresponsive to pilocarpine, our case series shows its inconsistency in clinical presentation. Conclusion: This report presents 1 case of systemic scopolamine toxicity, alongside unilateral mydriasis, adding confusion to the case given the expected bilateral mydriasis in systemic toxicity, and another case of pharmacological anisocoria secondary to exposure to scopolamine with an atypical reaction to pilocarpine. These cases highlight the importance of thorough history taking and the need to consider pharmacological causes in the differential diagnosis of acute anisocoria.

Anisocoria, a condition characterized by unequal pupil sizes, is most commonly physiological, with an estimated prevalence of around 19% in the general population [1]. However, the sudden onset of anisocoria can be alarming for clinicians, as its causes range from benign to life-threatening, necessitating a more extensive workup [2]. Adie’s [3] pupil, also known as tonic pupil, often presents as a unilateral large pupil in young women, with or without accompanying visual symptoms. A pharmacological cause, such as scopolamine – commonly used in transdermal patches to prevent motion sickness – can present with similar clinical characteristics [4]. Although scopolamine is prevalent as an anti-motion sickness patch, its side effect of pupil dilation is not well known among the general population or physicians. The first case demonstrates scopolamine toxicity, which might not necessarily result in bilateral mydriasis as would be anticipated but associated with a unilateral mydriasis due to direct contamination resulting in confusion in the clinical picture. The second case suggests that earlier studies, which supported the use of pilocarpine to differentiate anticholinergic effects from neurogenic causes of mydriasis, do not always reflect real-life clinical observations. The 2 cases illustrated in our report aim to enhance clinical awareness of drug-induced anisocoria and emphasize the importance of thorough medical history taking. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000545362).

A medical student in her 20s awoke with an elevated heart rate and dizziness. While on clinical duties, she noticed unilateral blurry vision. An ophthalmologist colleague observed mydriasis on her right eye but did not identify an urgent cause. The patient self-administered pilocarpine drops from the ophthalmology ward, which improved accommodation but showed no effect on the pupil size (see Fig. 1).

Later that evening, she consulted the emergency neurology department. A comprehensive neurological evaluation including an MRI followed and showed no abnormalities. Despite continued use of pilocarpine drops, her symptoms persisted without improvement.

After several doctors’ visits and examinations, the patient recalled hurriedly handling powdered scopolamine hydrobromide in a research laboratory the day before the onset of the symptoms and reported it to the doctor. Recognizing the consequences of scopolamine exposure, the clinical team attributed her symptoms to this incident. The tachycardia and dizziness subsided within 2 days, and 5 days later, her pupil size returned to normal without further intervention.

A female patient in her 40s presented with a 3-day history of blurry vision in her right eye and a dilated right pupil. The symptoms started the day after she returned from a 1-day sea trip. She reported no additional neurological symptoms.

On the first day of symptoms, she visited her local hospital where a CT scan of the brain was performed, revealing no abnormalities. She was given pilocarpine eye drops and was referred to our hospital. After multiple administrations of pilocarpine throughout the day, the pupil size returned to normal. However, the patient noticed pupil dilation again on the next day.

The patient was referred to our hospital for further ophthalmic evaluation. Aware of a similar case of unilateral mydriasis associated with scopolamine that occurred just a few days earlier and the common use of transdermal scopolamine for motion sickness, our medical team asked specifically about the use of scopolamine patches during her trip. The patient then disclosed having placed the scopolamine patch in front of her ears, on the right temple, to alleviate motion sickness symptoms.

Given the proximity of the patch placement to the affected eye and the time of its placement, combined with a lack of a neurological cause, the diagnosis of scopolamine-induced unilateral mydriasis became evident. The patient was sent home with instructions for monitoring and education about the effects of scopolamine. A week later, the patient reported a complete recovery.

Scopolamine, commonly used as a mydriatic and cycloplegic drug in ophthalmology, is from the same biosynthetic pathway as atropine [5]. Its antimuscarinic property paralyzes the sphincter muscle of the iris and the radial ciliary muscle of the lens, causing blurry vision and accommodation problems [6].

While there was systemic absorption of scopolamine in both cases, the unilateral dilation of the pupil was believed to have been caused by accidental contamination. The dose of exposure in the first case was believed to be higher, as tachycardia and dizziness were observed, implying scopolamine toxicity [7]. However, this did not manifest as bilateral mydriasis. Systemic effects of scopolamine were expected to affect both eyes, as in the case of bilateral mydriasis due to central cholinergic syndrome induced by scopolamine [8]. Therefore, contamination of the fingers, and subsequently the eye, was more likely the cause. In the second case, although the local transdermal effect of the position of the transdermal patch as a cause of the pupil dilation was not out of consideration, the unilateral mydriasis was still primarily suspected to have been caused by accidental finger-to-eye contamination after handling the patch so close to the eye.

Another clue that typically distinguishes a pharmacological cause secondary to an anticholinergic substance from a neurogenic cause is the failure of pilocarpine to constrict the pupil. However, this was inconsistent in this case series. Scopolamine, as a competitive antagonist, blocks the action of pilocarpine, preventing it from causing pupil constriction. A pilocarpine test is suggested in cases of unilateral mydriasis: if there is no impaired oculomotor nerve function or increased intracranial pressure, the failure of pilocarpine to constrict the pupil indicates a pharmacological cause [9, 10]. Conversely, pilocarpine can be used diagnostically for Adie tonic pupil: in a diluted form, it confirms a neurological cause of pupil dilation [11, 12]. While a protocolized pilocarpine test was not performed in the presented cases, patient history in the first case was in accordance with the characteristics of a pharmacological cause of anisocoria. In the second case, the interaction between pilocarpine and scopolamine was more complex. Initially, pilocarpine likely achieved pupil constriction by temporarily outcompeting scopolamine at the receptor-site, as according to the patient report, pilocarpine was administered multiple times in an attempt to constrict the pupil. The reversal could be explained by the long-acting nature of scopolamine, which can exert its effects on the pupil for up to 2 weeks [13], whereas pilocarpine-induced miosis typically persists for 4–8 h and rarely up to 20 h [14]. It is also possible that there was a repeated, inadvertent contact of scopolamine if the patch was not removed properly or if there was residual medication on the skin, which caused prolonged mydriasis.

In both cases, it took multiple clinical visits for the patients to recall their previous exposure to scopolamine. This highlights the importance of thorough medical history taking and awareness of the ophthalmic side effects of the drug in cases of isolated unilateral mydriasis without other significant findings. Such awareness can prevent unnecessary and expensive examinations and provide reassurance to the patient.

Written informed consent was obtained from the patient for publication of the details of their medical case. This report does not contain any personal information that could lead to the identification of the patient. The research was conducted ethically in accordance with the Declaration of Helsinki. Ethical approval is not required for this study in accordance with local or national guidelines.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

Leyan Li: investigation, resources, writing – original draft, and writing – review and editing. Lili Lian: resources and writing – review and editing. Rong Zhou: supervision, resources, and writing – review and editing.

Present address: Leyan Li, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.