An eccentric presentation of transient bilateral mydriasis after botulinum toxin injection: A case report

Abstract

Introduction

Botulinum toxin (Botox) can be used to manage strabismus due to its efficacy in inducing muscle paralysis by blocking acetylcholine release. Botox is an important treatment for many conditions in ophthalmology; however, clinicians must be aware of its potential complications, such as mydriasis. Mydriasis is defined as dilation in the pupils, and it can be divided into two subsets: transient and persistent mydriasis.

Case presentation

This report presents a case of a 4-year-old child having esotropia (ET) with an angle of 30 Prism Dioptre (PD) and Inferior Oblique muscle Overaction (IOOA). The patient was scheduled for Botox injection to correct ET and IOOA and developed transient bilateral mydriasis.

Discussion

Botox is a valuable therapeutic intervention in pediatric ophthalmology. A potential side effect of it is transient mydriasis, which developed in this patient. Interestingly, a higher dose of Botox injected a second time didn't result in mydriasis, which depicts a potential variability in patient responses to Botox. The mechanisms behind this adverse effect and its occurrence regardless of the dose remain unclear, but proposed hypotheses suggest that toxin diffusion could impact nearby structures, such as the ciliary ganglion or pupillary sphincter muscle, leading to pupil dilation. In addition, this case highlights the importance of vigilant post-injection monitoring. Further research and investigation are warranted to elucidate the possible underlying mechanisms in order to provide guidance for clinical practice.

Conclusion

Collectively, our results confirm that the patient developed transient bilateral mydriasis as a result of Botox injection.

Highlights

• •Botulinum toxin (Botox) is commonly used to treat strabismus. Botox injections could be associated with mydriasis as an uncommon complication.
• •Mydriasis is defined as pupil dilation and can be divided into persistent and transient sub-groups.
• •Patients with persistent mydriasis tend to have pupillary dilation for long periods, whereas transient mydriasis is a temporary dilation.
• •The actual mechanism of such mydriasis is still unknown, and further research could shed light on the possible causes.

1. Background

Botulinum toxin (Botox) is commonly used in the treatment of strabismus. It acts by inhibiting the release of acetylcholine, which is a neurotransmitter that facilitates muscle contraction. This results in a transient palsy of the muscle injected [[1], [2], [3]]. Ptosis can occur after medial rectus injection due to levator exposure to the toxin [[3], [4], [5], [6]]. Other severe complications of Botox injections into the extraocular muscles (EOM) include globe perforation, necrotizing fasciitis, and angle-closure glaucoma [3,6].

Cases of botulinum toxin-related mydriasis have been reported in the literature [[7], [8], [9]]. The actual mechanism is still unknown, and further studies could elucidate the cause of persistent and transient mydriasis. Here, we report a case of a patient who developed transient bilateral mydriasis after receiving a single dose of Botox injection in both eyes.

Our work has been reported in line with the SCARE Guideline's latest criteria [10].

2. Case presentation

A 4-year-old child presented to the outpatient clinic at a hospital with ET and IOOA and wearing +4.00 glasses that had been prescribed a few months ago in another hospital.

Inward deviation was noticed by the parents at the age of 1 year. Her examination showed ET with an angle of 50 PD at a distance and near while wearing glasses. The patient was otherwise medically and surgically free. After multiple follow-up visits, the patient was diagnosed as partially accommodative ET with IOOA. Her parents were interested in trying Botox injections before any surgical intervention. Thus, a five international unit (0.1 mL) of Botox (botulinum toxin type A, Allergan pharmaceuticals, Ireland) injection was injected bilaterally into the medial rectus and inferior oblique muscles under general anesthesia using a 27-gauge needle. At her first check-up visit, which was 1-week postoperative Botox injection, her examination showed ET with 25 PD at a distance and near.

Further, she had developed bilateral mydriasis (Fig. 1). The right and left pupils measured 5.50 mm and were fixed, with no direct or consensual response to light, and they failed to dilate further in scotopic conditions. Nonetheless, the patient was not on any drugs that might account for the dilated pupils. The patient had no previous history of ocular surgery or botulinum toxin injection. Best corrected visual acuity was 20/20 in both eyes. Biomicroscopic examination of the anterior segment was normal. Intraocular pressure was 15 mmHg in both eyes, and there was no abnormality in extraocular movements. A thorough dilated fundus examination was normal; there were no other neurological abnormalities.

Fig. 1.

Bilateral mydriasis seen on the 1st post-Botox injection follow up visit (pupil size 5.50 mm).

Another follow-up visit two weeks later revealed that the patient still had the same finding.

Ten weeks post-operation, both eyes had regular, round, and reactive pupils that measured 2 mm (Fig. 2). Thus, this confirmed that she had transient mydriasis. However, the patient was still having esotropia with an angle of 35 PD. The decision was to perform another Botox injection in both eyes while increasing the dose to 7.5 international units (0.1 mL) into the medial rectus and inferior oblique muscles and under general anesthesia. This time around, the patient didn't develop mydriasis during any of her follow-up visits over a period of three months.

Fig. 2.

Round and regular pupils seen ten weeks post-Botox injection (pupil size 2 mm).

3. Discussion

Strabismus, also known as squint, is a form of misalignment of the visual axis, and it is estimated to affect 1 % to 3 % of children [11]. Botox is a commonly used substance to treat strabismus, resulting in muscle contraction and transient palsy in the injected muscle [[1], [2], [3], [4]]. It has been reported before that Botox injections could be associated with complications including, but not limited to, ptosis, perforation of the globe, and angle-closure glaucoma [[3], [4], [5], [6]]. Mydriasis was reported as another complication of Botox injections [9].

Mydriasis can be divided into persistent and transient sub-groups. Patients with persistent mydriasis tend to have dilated pupils for long periods, whereas transient is a temporary dilation in the pupil [7]. Transient mydriasis has been reported after injection with botulinum toxin into EOM, mostly the lateral rectus muscles [7]. In our case, we reported transient mydriasis after Botox injection into the medial rectus and inferior oblique muscles. Experimental retrobulbar injections in animals have also yielded a finding of transient mydriasis [7,9,12].

Furthermore, two cases of persistent unilateral mydriasis have been reported [7,8]. Postulated mechanisms that led to this phenomenon include the involvement of the ciliary ganglion through toxin diffusion, which results in impaired accommodation and meiosis. Injury to the parasympathetic neuromuscular junctions in the pupillary sphincter muscle or simply intraocular diffusion of the toxin into the pupillary sphincter could also play a role [7,8].

It was previously reported that an 11-year-old boy developed transient bilateral mydriasis after being poisoned with foodborne botulism [13]. This is clear evidence that botulinum toxin can cause mydriasis. A case of a 3-year-old boy with an angle of more than 60 PD was reported to develop persistent unilateral mydriasis after receiving 1.25 international units of Botox (botulinum toxin type A, Allergan pharmaceuticals, Ireland) [7].

However, in our case, we reported transient bilateral mydriasis, which resolved a few weeks later. Interestingly, such a finding was an isolated incident in our patient, as she underwent an even higher dose of Botox injection bilaterally in the same medial rectus and inferior oblique muscles a second time around. Yet she didn't develop mydriasis in either eye. The very same eyes didn't react as they did after the first instance of Botox injection, although the dose was higher with precisely the same EOM involvement, the same methods, and the same operators. We speculate that the toxin may have reached the ciliary ganglion through diffusion. Moreover, it is possible that the needle inadvertently advanced beyond the muscle into the intraconal space, and the botulinum toxin affected the ciliary ganglion, which is situated in the intraconal space. Those possible mechanisms may explain why this complication doesn't happen with each patient receiving Botox injection and why some eyes are affected unilaterally while others had the effect bilaterally, as in our case, regardless of the dose. A case of unilateral transient mydriasis after cosmetic Botox injection was reported, and the authors believe that the cause of such complication happened because botulinum toxin had been administered at a high dose in the affected eye compared to the other eye. This is against what our case demonstrated; injecting a higher dose in the second operation didn't result in the development of any complications [14].

Alternatively, the toxin could have acted at the parasympathetic neuromuscular junctions of the iris's sphincter pupillae, but this is less likely, as it would typically require either an intraocular injection or an unusual idiosyncratic reaction to the toxin. This elucidates that a patient's eyes can react differently when injected with the same Botox material. To our knowledge, such a case has not been reported yet in the literature. The patient was further monitored, and no further complications have occurred.

4. Conclusion

Collectively, this case report presented a case of a patient with non-recurring bilateral mydriasis as a result of a botulinum toxin (Botox) injection. Ten weeks post-injection, the patient recovered from the mydriasis. Her pupils were round and had a regular shape, confirming that the patient had transient mydriasis as there were no other neurological abnormalities in the examination, and the patient was not using any medication that might account for possible drug-induced mydriasis. No specific clinical information from her history or examination suggested that another tangible factor could have been a culprit. Post her second Botox injection into the same EOMs, such mydriasis never occurred again.

CRediT authorship contribution statement

• Rana Alhumaemydi: Study concept, data collection, interpretation and writing the paper.

• Abeer Alkhodier: Study concept, data collection, interpretation and writing the paper.

• Ismail Alghamdi: Study concept, data collection, interpretation and writing the paper.

Parental consent for minors

Written informed consent was obtained from the patient's parents/legal guardian for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Ethical approval

This case report is exempt from ethical approval as it involves a single patient case that is anonymized and does not include any identifiable personal information.

Guarantor

Dr. Rana Alhumaemydi.

Funding

None.

Declaration of competing interest

The authors declare no conflict of interest.