A Randomized, Controlled, Non-inferiority, Crossover Trial on the Efficacy of Isolated Periocular Botulinum Toxin A Injections Versus Conventional Periocular and Adjunctive Lower Facial Injections in Hemifacial Spasm

Hemifacial spasm (HFS) is an uncommon neurological disorder with a profound impact on patients’ lives. It is characterized by involuntary, unilateral spasms of facial muscles, typically originating around the eye (periocular area) and gradually progressing to the cheek, mouth, and chin. The condition is often chronic and tends to worsen over time. Many patients experience visual impairment due to eyelid spasms obstructing their vision, leading to a loss of confidence in social interactions and significantly affecting their emotional well-being and professional lives. Although not life-threatening, HFS is a condition that clearly “debilitates daily life,” making effective treatment critically important.

Botulinum Toxin: The Standard of Care Requiring Lifelong Injections

For decades, Botulinum Toxin A (BoNT-A) injections have been the mainstay of effective treatment for HFS, providing clear, temporary relief from muscle contractures. However, this modality has its limitations:
* It requires repeated injections every 3–4 months.
* It constitutes a significant burden for both the patient and the healthcare system.
* Injections into the lower facial muscles can lead to adverse effects, such as drooping of the mouth corner (oral commissure), facial asymmetry, and difficulty speaking.

In standard clinical practice, many physicians have long administered injections to both the periocular and lower facial areas according to a “conventional protocol.” However, a key clinical observation was made during the COVID-19 pandemic: the mandatory use of face masks led to the omission of lower facial injections, yet patients’ symptoms remained well-controlled. This prompted a crucial question: “Is it necessary to inject botulinum toxin into the lower face of every HFS patient?”

Research That Challenges the Conventional Standard

The study, “Efficacy of isolated periocular botulinum toxin A injections versus periocular and adjunctive lower facial injections in hemifacial spasm,” published in *Annals of Medicine* in 2025, was conducted by a team from the Department of Ophthalmology, Faculty of Medicine Siriraj Hospital. The research, led by Lecturer Akkarawich Eiamsam-ang, MD, Professor Niphon Chirapapaisan, MD, and Professor Wanicha Chuenkongkaew, MD, was designed as a Randomized, Controlled, Non-inferiority, Crossover trial.

A total of 46 HFS patients received two treatment protocols at different times:
1. Isolated periocular injections (Botox administered only to the muscles around the eye).
2. Conventional injections (Botox administered to both the periocular and lower facial areas).

The primary objective was to demonstrate that the isolated periocular injection method was “non-inferior” to the conventional method in controlling HFS symptoms.

Results That Shift the Clinical Paradigm

The study revealed the following:
* The isolated periocular injection method was non-inferior to the conventional method in controlling HFS symptoms, including those in the lower face.
* There were no statistically significant differences in patient-reported symptom scores (VAS), disease severity scales (HSGS, SMC), or quality of life measurements (HFS-30) between the two methods.
* The adverse effect of a drooping mouth corner was observed exclusively in the group receiving conventional injections.
* The isolated periocular method required a lower total dose of botulinum toxin, involved fewer injection sites (reducing pain), and resulted in higher patient satisfaction.

In other words:
– Efficacy was comparable.
– The safety profile was superior.
– Patients reported a more “natural” facial appearance and function.

From Research Data to Real-World Patient Impact

Following the COVID-19 pandemic, the research team observed that over 85% of patients continued to choose the “isolated periocular injection” method, even when the option for conventional treatment was available. The primary reasons cited were the absence of facial distortion and the ability to speak, chew, and smile naturally, which enhanced their confidence in social settings. Furthermore, this refined approach was found to reduce the total annual cost to the healthcare system by over 19%—a significant saving for clinics managing a large number of long-term HFS patients.

Today, the isolated periocular injection protocol is implemented as the standard of care for all new HFS patients treated at the Ophthalmology clinic at Siriraj Hospital.

This research was presented internationally and received the 1st Place Award for Outstanding Research at The 12th Asian Neuro-ophthalmology Society Meeting in the Hong Kong Special Administrative Region of the People’s Republic of China.

Implications for the Era of Precision Medicine

This research does more than simply change injection sites; it shifts the entire treatment paradigm from a “one-size-fits-all” approach to one that is “precisely tailored to the individual patient.” This embodies the core principle of Precision Medicine in clinical practice: treating the “person,” not just the disease.

Conclusion

Hemifacial Spasm is a chronic condition that, while not fatal, silently erodes a patient’s quality of life. This pivotal research from our Thai medical team demonstrates that sometimes, a “lesser” intervention can produce a more fitting and superior outcome for the patient. It marks a significant step for a medical practice that asks not only, “What is theoretically best?” but more importantly, **”What is best for this patient in their actual life?”

Research Team
Lecturer Akkarawich Eiamsam-ang, MD
Professor Wanicha Chuenkongkaew, MD
Dr. Manassawee Joradoln, MD
Ms. Yanee Mukdar, BSc
Professor Niphon Chirapapaisan, MD
Lecturer Natthapon Rattanathamsakul, MD
Mrs. Phakinee Rueangcharin, BSc
Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University