Diplopia Secondary to Neurotoxin Injections: Prevention, Diagnosis, and Management

By Tara Delle Chiaie, DNP, MSN, FNP-BC, APRN

Tara is the owner of Delle Chiaie Cosmetic Medicine and Delle Chiaie Concierge Medicine as well as the founder and principal instructor of DCCM™ Academy, an ever-expanding training school for the next generation of aesthetic injectors. She is also the author of the book, Essentials of Neuromodulation, published by Elsevier.

J Clin Aesthet Dermatol. 2024;17(3–4 Suppl 1):S30–S36.

Funding: No funding was provided for this article.

Disclosures: KOL Candela Medical and National Trainer for Allergan.

In a world where the quest for beauty is often synonymous with the pursuit of youth, neurotoxin injections have emerged as a favorite elixir to fight aging while enhancing beauty; however, a concerning trend is on the rise resulting from these procedures; diplopia (double vision). Diplopia is derived from two Greek words: diplous, meaning double, and ops, meaning eye.¹ Although official statistics for the development of diplopia hover around two percent, this number is almost certainly the tip of the iceberg.² The realm of cosmetic enhancements remains largely uncharted, with many incidents going unreported due to the lack of mandatory disclosure, official registration, and state regulations. As more individuals experience this unsettling side effect, the need to prioritize the safety of cosmetic treatments becomes ever more pressing. This article delves into the delicate interplay of technique, product, and anatomy, illuminating the rising concern of diplopia and emphasizing the indispensable role of expertise in cosmetic medicine. The purpose of this manuscript is to bolster practitioners’ understanding of this complication, enrich their grasp on the extraocular muscles, and provide insights into the causes of diplopia while establishing a gold standard in the prevention and management of this rare adverse event.

In rare cases, botulinum toxin injections may result in intraorbital effects, including diplopia, accommodation difficulties, retinal detachment, glaucoma, corneal irritation, and corneal exposure.³ Diplopia, colloquially known as double vision, is a rare yet devastating side effect associated with cosmetic neurotoxin procedures aimed at reducing dynamic rhytids in the upper third of the face. Diplopia can arise from genetic predispositions, trauma, or the onset of conditions like strokes or tumors, as well as inadvertently (or iatrogenically) through the misplacement or diffusion of neurotoxins into the extraocular muscles. Most adverse events secondary to neurotoxin injections can be prevented through heightened anatomical awareness and meticulous injection techniques that consider the entire anatomical framework rather than solely the targeted muscles in the treated area.^3–5

Patients who develop diplopia following neurotoxin injections suffer profoundly, as this is an extremely distressing adverse event impacting daily activities such as driving, socialization, and working. In some cases, diplopia can coexist with a medial or lateral rectus palsy, causing the eye to misalign in an unnatural, deviated position.⁶ See Figures 4 and 5 demonstrating what a lateral and medial palsy look like in the left eye. The distinguishing factor between isolated diplopia and diplopia accompanied by a rectus palsy lies in the clinical positioning of the eyes. While double vision typically arises from a weakened extraocular muscle, a palsy accompanying diplopia results from the complete paralysis of such a muscle.^6,7 A thorough examination encompassing medical history, surgical history, injection procedures, proper handling of the drugs such as dilution, storage, and preparation is paramount in prevention and management.

The literature identifies three types of eye movement disorders: strabismus, nystagmus, and paralysis of specific extraocular muscles.⁸ Post-cosmetic neurotoxin injections, the visual impairment is often attributed to the weakening or complete paralysis of one of the extraocular muscles. Genetic or prior cases of strabismus or nystagmus should ideally be identified during the patient’s comprehensive medical examination prior to any treatment. If post-treatment visual dysfunction arises, it is essential to first assess the treatment dose and technique before delving into the patient’s structural and neurological eye functions. Post-marketing data indicates an inherent risk of developing diplopia post-neurotoxin injection, especially around the lateral canthal lines, though other regions are not exempt from such risks.⁹

Understanding Ocular Anatomy

Normal vision perception requires high-level functioning of the ocular motor systems.¹⁰ The ocular motor systems include the extraocular muscles as well as cranial nerves III, IV, and VI that assist in aligning the eyes for clear vision (Figure 1).⁸ The ocular motor system controls the position and movement of the eyes to focus on an image or object which is considered to be the visual target. The human eye possesses seven extraocular muscles that enable gross eye movement, facilitating object tracking and ensuring clear vision. These seven extraocular muscles include the medial and lateral rectus muscles, the inferior and superior oblique muscles, the inferior and superior rectus muscles, and the levator palpebrae superioris. With the exception of the levator palpebrae muscle, these muscle pairs work reciprocally; as one contracts, the antagonist counterpart relaxes.

The roles of these muscles are as follows (Table 1):

1. Medial and Lateral Rectus Muscles: These are responsible for horizontal eye movements. The medial rectus muscle pulls the eye inward (adduction) towards the inner canthus, while the lateral rectus muscle pushes it outward (abduction) towards the outer canthus (Figures 2 and 3).^8,10,11
2. Superior and Inferior Rectus Muscles: This pair of muscles manages vertical eye movements. The inferior rectus muscle depresses the eye, pulling it downwards, whereas the superior rectus muscle elevates the eye, directing it upwards towards the brow’s medial section (Figure 2).^8,10,11
3. Superior and Inferior Oblique Muscles: These muscles rotate the eye about its axis. Intorsion is the eye’s inward rotation, moving the upper part closer to the nose. In contrast, extorsion involves the top of the eye twisting away from the nose. The inferior oblique muscle is responsible for extorsion whereas the inferior oblique muscle is responsible for intorsion (Figure 2).^8,10,11

Normal, optimal vision is referred to as “binocular vision.” Binocular vision is when both eyes are working in harmony, capturing images that the forebrain then fuses from singular images in each eye to one image between the two. Clear vision is reliant on the paired extraocular muscle’s proper function. Any disruption in this complex system may lead to diplopia, which can present alone or with a rectus palsy affecting one of the extraocular muscles. Post-marketing data states that there is a relative risk to develop diplopia after cosmetic neurotoxin, specifically the lateral canthal lines; however, other areas are not without the same risk.^2,9

The potential ramifications of diplopia and other complications following neurotoxin injections can include litigation, underscoring the importance for injectors to comprehend the anatomy of the treatment area. Aesthetic injectors must not only grasp anatomy and the drugs they administer, but also master the art of informed consent, patient selection, and injection technique. Staying poised allows providers to maintain a trusting patient relationship in the event of a complication. The most natural way to stay poised in a crisis is to be informed. The primary objective in cosmetic medicine is the prevention of adverse events; however, should a complication occur, the provider must be adept at managing the problem and the relationship with the patient. In the event of a complication, an extensive understanding of the human body, extending beyond cosmetic medicine, is crucial for accurate diagnosis and effective treatment.

Prevention

Risk assessment and patient selection. Effective risk mitigation in cosmetic procedures, particularly those involving neurotoxins, begins with appropriate patient selection, underscored by an exhaustive medical examination. Certain individuals, owing to genetic factors, previous conditions, or the interplay of multiple health variables, may exhibit an inherent susceptibility to diplopia when undergoing neurotoxin injections. Recognizing and understanding this heightened sensitivity is crucial to patient selection. A patient’s inherent susceptibility demands greater caution during the treatment, enhanced post-treatment monitoring, and potentially modified dosing strategies. A judicious risk assessment, grounded in detailed patient history and meticulous examination, is the cornerstone of ensuring patient safety and optimizing treatment outcomes. The objective is to identify any underlying vulnerabilities that might predispose a patient to complications following neurotoxin injections. A comprehensive medical history serves as the foundation to this assessment.

Key elements that should be established when collecting a patient’s history include the following:

1. Previous facial trauma: Past incidents may affect the structural integrity of the facial musculature and adjacent structures. This could influence how the neurotoxin interacts with the tissue.
2. Visual and ocular history: Knowledge of conditions like existing diplopia, strabismus, nystagmus, or any irregularities in baseline visual acuity is essential. Such conditions might hint at compromised ocular functionality or pre-existing muscle imbalance which can be exacerbated by neurotoxin administration and enhance the possibility of diffusion. Prior history of diplopia post cosmetic neurotoxin.⁴
3. Neurological considerations: Identification of global apraxia or ocular motor apraxia is vital. Apraxia represents a disruption in the brain’s ability to execute coordinated movements. The presence of such conditions could indicate an elevated vulnerability to the side effects of the toxin and can be limited to an oculomotor apraxia causing a failure of the eyes to track left to right smoothly.¹²

Pre-treatment documentation. In the contemporary cosmetic clinical setting, detailed documentation, both visual and written, stands as an indispensable tool to any provider. Visual and written documentation provide a comprehensive pre-treatment record, while facilitating post-treatment evaluations and discussions with patients further enhancing a comprehensive approach to cosmetic treatments.

Photos. Photos are imperative to treatment. Cosmetic providers must capture clear photos of patients in a resting state and while in motion with their hair pulled back and makeup cleaned from the skin. These photographs serve as a baseline to compare with post-treatment results.

Videos. A short, three-second video capturing facial movements can provide a dynamic view of the patient’s expressions and potential asymmetries. This aids in the post-treatment assessment and any necessary corrective measures.

Documentation of pre-existing asymmetry. Before commencing cosmetic treatments, providers should consider any existing facial asymmetry. Often, patients might not be aware of, or may simply overlook, their unique asymmetries. Finding a subtle way to note the asymmetries is extremely important. Use phrases such as “this eyebrow is a bit higher than the other side.”  Highlighting the positive versus the negative can help your patient maintain self-confidence in an otherwise vulnerable scenario. Post-treatment, there is always the possibility of a patient developing amnesia, forgetting their pre-treatment appearance. This underscores the importance of thorough documentation and open dialogue with the patient. Eyelid and eyebrow asymmetry is commonplace; however, grossly under noticed by patients without the skillful providers call to attention. A brief assessment should also be performed of the eye and the alignment prior to initiating treatment.

Injection technique. In order for diplopia to occur, neurotoxin must get to the highly protected area where the extraocular muscles reside. This entails the neurotoxin navigating through several tissue layers, including the hypodermis, the orbicularis oculi, and the orbital septum. The hypodermis is primarily composed of fat and connective tissues and acts as a cushion, protecting the body from injuries. The orbicularis oculi is a thin, flat muscle in the facial region that surrounds the eye. This muscle is primarily responsible for eyelid closure. The orbital septum is a membranous barrier that segregates the eyelid’s contents from the orbital contents. It is semi-permeable and houses perforations, facilitating the transit of the supratrochlear and supraorbital nerves, arteries, and veins from the orbit to the forehead. These specific perforations are identified as the superior orbital foramen.

Effective cosmetic injections are not merely about a standard dose or targeting specific muscles; mastery necessitates a holistic comprehension of both the localized and surrounding anatomy. Cosmetic providers must move beyond the static cookie-cutter approach and begin exploring in greater detail the underlying anatomy and the greater systems in which are impacted by cosmetic injections. A competent cosmetic provider will also arm themselves with a global understanding of cause and effect by comprehensively understanding the anatomy in and around the targeted area for treatment. Natural safe zones for the face exist and staying in these zones can help injectors prevent or reduce the risk of adverse events.³ Recognizing the depth and the relation to the orbital rim are vital landmarks when administering neurotoxins to reduce the occurrence of diplopia.

The orbicularis oculi, when targeted for crow’s feet treatment, is considered to pose the most significant risk for diplopia onset with a lateral rectus palsy (Figure 4).^11,13 While injecting, maintaining an angle between 30 to 45 degrees ensures effortless insertion and optimal depth.^3,14 Directing the needle away from the eye’s globe can assist in the proper dispersion of neurotoxin to the orbicularis oculi versus aiming towards the globe and having the product diffuse through the septal barrier and cause double vision with or without a palsy.¹⁴ Injections should be placed at about 1.5cm from the orbital rim (Figure 6).^3,14  A prudent move is to apply digital pressure on the orbital rim to diminish the odds of diffusion through the orbital septu.³ Some research suggests that if a neurotoxin is inadvertently introduced into the arteries in the lateral canthal region, it might pave the way for the diffusion of the toxin to the extraocular muscles, either via the arterial or venous systems.⁶

Diagnosis and Assessment

To properly diagnose and treat post-neurotoxin injection complications, an understanding of the affected anatomical structures and their functions is essential. Cosmetic providers should have the expertise to develop a range of differential diagnoses, looking beyond mere symptoms like eyelid ptosis or palsy being exclusively injection-related. A holistic view of the patient’s overall condition is pivotal. For instance, while rare, a patient could experience a stroke coinciding with the time of injections. Thus, it is crucial for practitioners to possess comprehensive knowledge that extends beyond the confines of cosmetic procedures. Being proactive and accessible post-injection is an integral part of a practitioner’s duty. Immediate availability ensures timely interventions, which can be critical for addressing complications. When the cosmetic provider guarantees the patient that there is always someone available for post-treatment queries, you can steer them away from self-diagnosis through search engines like Google, which can sometimes escalate anxieties and lead to misinformation and a fractured patient provider relationship. Developing a sound consult process and a thorough informed consent process will deter your patients from self-diagnosis, anxiety, and losing the patient down a rabbit hole of Google and the emergency room. Should a patient, driven by anxiety or misinformation, rush to the emergency room, they might undergo a gamut of extensive and invasive tests for conditions like stroke. Not only does this put an unnecessary strain on the healthcare system, but it could also be traumatic for the patient and amplify the complications associated with the original injection. Proper patient selection and adequate pre-injection briefing can be instrumental in mitigating such scenarios.

Assessment protocols. Starting point. Initiate your assessment inward, focusing on the eye’s iris and lid position. Compare both eyes for any discrepancies then work your way outward and upward.

Functional assessment. Observe the patient’s reactions as they squint or raise their eyebrows. This gives a perspective on the dynamic changes and potential issues that might need addressing.

Eyelid folds. Assess the eyelid’s natural folds, both at rest and during motion. These folds can provide insights into the structural anatomy and possible post-treatment outcomes.

Muscle engagement. Particularly when treating the frontalis muscle and the glabella complex, it is vital to understand the natural behavior of the muscles. Some patients might subconsciously engage their frontalis muscle even at rest. This subconscious engagement is often a compensatory mechanism in patients with baseline brow or eyelid ptosis. The frontalis helps lift the eyelids or brows, enhancing peripheral vision; therefore, should not receive frontalis injections.

Visual acuity/peripheral assessment. Before treatment, inquire about the patient’s visual acuity. Baseline acuity should be measured with a Snellen chart. The average patient will not know their baseline visual acuity, making the brief Snellen exam for visual acuity a proper baseline examination. This can provide insights into any underlying conditions or concerns. Secondly, conduct a straightforward gaze test, guiding the patient’s vision using a finger. This will help in assessing any existing rectus palsy or other ocular motility issues. In summation, the cornerstone of successful treatment lies in meticulous pre-treatment evaluations.

Management

Managing a visual adverse event following neurotoxin injections. Should the worst-case scenario occur and a patient suffers from a visual disturbance post neurotoxin injection, a brief neurological exam will be beneficial in an effort to narrow down the differential diagnosis and begin the proper treatment protocol. The brief neurological exam will mirror much of what was done prior to cosmetic injections creating a compilation of baseline and post treatment data to enhance the accuracy of the diagnosis.

Immediate assessment. Begin with a comprehensive history intake to understand the nature and onset of the symptoms. Time is of the essence when a patient suffers from a visual disturbance. Ensure that the disturbance is not related to a non-injection cause, such as stroke or other neurologic disorders which will need immediate emergent work up which will likely be outside your clinic’s ability.

Conduct a detailed neurological examination, which includes the following:

1. Visual acuity. Test the sharpness of the patient’s vision for both near and distance. The first step after a patient complains of a visual disturbance is for the provider to perform a visual acuity exam.^4,12,15 Having a baseline visual acuity is of great value and improves the quality of the data of the same exam performed after an adverse event.  The baseline will be your benchmark to return to normalcy.
   • How to perform a visual acuity test:
     • Place a hand-held visual acuity card (SNELLEN CHART) 14 inches in front of the patient’s right eye while the left eye is covered. The patient should wear his or her usual corrective lenses if they have such devices. Ask the patient to read the lowest line on the chart (20/20). If the patient cannot read at the 20/20 line move up the lines until they can successfully read the line items correctly at 100%.
     • Repeat the process for the left eye.
     • Document.
2. Pupillary light reflex (CN II and III); Check for size, position, shape, and reactivity to light.
   • • Reduce the light in the treatment room as much as possible.
     • Shine a penlight on the bridge of the patient’s nose so that you can see both pupils without directing light at either of them. Check that they are the same size.
     • Next, move the penlight so that it is directly shining on the right pupil, and check to see that both pupils have constricted to the same size.
     • Move the penlight back to the bridge of the nose so that both pupils dilate.
     • Repeat step 3.
     • The last step in pupillary function is to move the penlight rapidly from the left pupil to the right; the pupil size should not change. Drift the light back to the left pupil; again, the pupil size should remain constant. Repeat this drifting penlight maneuver several times to be sure there is no consistent tendency for the pupils to be larger when the light is directed at one eye than when it is directed at the other one.
     • Document.
3. Visual field testing or peripheral fields test. Determine if there is a loss in any visual field and then document.
   • How to perform a peripheral fields test:
     • Have the patient cover their left eye.
     • Stand facing the patient from roughly two arm’s lengths away, stretch your arms forward and to the sides so that your hands are at about “1:30” and “10:30” and just barely visible in your own peripheral vision. They should be the same distance from you and the patient. Hold your index finger on each hand extended. Rapidly wiggle the finger on either the left, right, or both hands, and ask the patient to identify where the movement occurs while looking directly at your nose.
     • The next step will be to move your hands down to roughly “4:30” and “7:30” and test again.
     • Document.
4. Eye movements
   1. • First observe the patient’s eyelids for ptosis and the general scleral show of the eyes.
      • Have the patient fixate on your finger held about two feet away, in the vertical and horizontal midline. Observe for fluid horizontal movements of both eyes in unison horizontally and vertically.
      • Ask the patient to avoid any movement of the head but to continue watching your finger as you slowly move it to the patient’s right.
      • Observe the smoothness and range of the patient’s eye movements. Both eyes should be able to cross midline and then return to baseline
      • Keep your finger at the far right of the patient’s gaze for several seconds while observing for nystagmus.
      • Move your finger slowly to the patient’s left and repeat the observations.
      • Return your finger to the vertical and horizontal midline, then move it slowly up, repeating the observations. Then move your finger slowly down and repeat the observations. As the patient looks down, the examiner should hold the patient’s upper eyelid to prevent the eye from being covered and potential palsy obscured.
      • Finally, return to the midline position, and move your finger diagonally down and to the left; then return to the midline and move your finger down and to the right

Once you feel confident with your diagnosis of diplopia with or without a rectus palsy, the following treatment options are available:

1. Observation: If the visual disturbance is mild and the patient is not severely affected, you may choose to monitor the patient over time. The effects of the neurotoxin will wear off after a few weeks to months.
2. Eye patch: For some patients, wearing an eye patch can help alleviate symptoms by blocking the double vision.^5,13
3. Referral: In cases where a definitive diagnosis cannot be made, or if there are concerns about other potential causes for the disturbance, refer the patient to a neurologist or ophthalmologist/oculoplastic surgeon for a more comprehensive evaluation. Evidence suggests that neurotoxin injections in the antagonist muscle are beneficial at creating balance and helping to restore vision and pupillary alignment.^4,5,7,13,16 This would need to be performed by an oculoplastic surgeon or specialist.

Throughout diagnosis and treatment, ensure that the patient understands the potential duration of the symptoms, what they can expect, and the possible outcomes. Open communication is crucial for providing emotional healing, reassuring the patient throughout the process, and offering education and evidence to support your diagnosis and treatment plan.¹⁴ Additionally, thoroughly document every step of the evaluation, treatment decisions, and patient communications in the medical record. This is essential for medical legal reasons and for tracking patient progress. Having a baseline level of data helps to chart the progress in the resolution of the problem. Following treatment of the diplopia, regularly monitor the patient by scheduling follow-up visits to evaluate the course of the symptoms and decide on any changes to the management plan. In person exams are ideal given the physical nature of the exams needed. Based on the adverse event, it is prudent to revise the informed consent documents for future patients, ensuring that they are made explicitly aware of the rare risks associated with the procedure. All consents should be a living document with constant revision based on experience and patient feedback.

Conclusion

At this time, the literature suggests that all patients who have experienced blurry vision post neurotoxin injection have completely returned to baseline, either with intervention or without intervention.³ Given the rapid growth of novice injectors entering the field, coupled with increasing consumer awareness, consumer demand, and a failure of regulations and standardized accredited education, the number of adverse events secondary to neurotoxin injections may continue to rise. Based on historical trends, one could postulate that the incident rate of diplopia will rise in tandem with the growth of the industry.

In our exploration of double vision as an adverse event following neurotoxin injections, the criticality of a profound understanding of the intricate anatomical structures and their interactions has been underscored. Double vision, although a relatively rare complication, carries significant ramifications for the patient, not only in terms of ocular discomfort but also potential psychological distress, decreased quality of life, and functional impairments. It behooves practitioners, irrespective of their level of experience, to have a comprehensive grasp of the underlying causes and to continuously update and refine their techniques and knowledge base.⁷ Further training in neurotoxin injection techniques as well as ocular anatomy will help to prevent similar complications in the future.^3,17 The mere possibility of inducing double vision and its subsequent implications underscores the imperative need for a rigorous approach to training, adherence to best practices, and ongoing learning. As the field of cosmetic interventions continues to evolve, the dynamics between patient expectations and optimal outcomes become even more entwined, making it essential for practitioners to be at the pinnacle of their craft. It is not just about mitigating risks, but rather, about championing an ethos of excellence. This sense of urgency to delve deeper, learn more, and ensure patient safety and satisfaction cannot be overstated.

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