Dry Eye Syndrome Due to Botulinum Toxin Type-A Injection: Guideline for Prevention

Abstract

Dry eye syndrome is a potential complication of botulinum toxin type-A injection (BTX-A) into the lateral canthal rhytids (crow's feet). The early manifestations of this syndrome are subtle and are rarely reported to the treating physician. A guideline for early detection of dry-eye state is proposed, in order to avoid more troublesome adverse effects that may develop with repeated injections of BTX-A into the crow's feet region. If suspected early, clinical manifestations remain minor and are reversible. However, delayed diagnosis may lead to troublesome and persistent symptoms. A novel and practical grading scale of lower eyelid snap-back and distraction tests is offered that helps in documenting patient's clinical progress and in deciding when BTX-A injections should be delayed or discontinued.

Introduction

Dry eye syndrome due to botulinum toxin type-A (BTX-A) injection for treatment of blepharospasm or after blepharoplasty and peri-orbital surgery has been previously reported in literature.^1–12 In contrast, dry-eye state due to BTX-A injection into the lateral canthal region for correction of crow's feet has received little attention.³ In comprehensive studies such as the “Botox Consensus Group,” no reference is made to dry eye syndrome.¹³ A more recent publication on causes of dry eye syndrome is also remiss in identifying BTX-A injection as a possible cause of this condition.⁷

Discussion

Our clinical observations for the past 11 years indicate that persistent signs and symptoms of dry eye syndrome frequently develop when BTX-A is injected regularly into the crow's feet region. The earliest symptoms include occasional eye irritation and foreign body sensation accompanied by mild intermittent tearing particularly in air-conditioned or dry and windy environments. If examined closely, very subtle blink dysfunction and lagophthalmos may be detected at this early stage that may be classified as “mild” with a grade of 1+ (Figure 1). These early symptoms and signs are typically either ignored or are self-treated by patients with over-the-counter eye lubricants and moisturizers with good relief. If BTX-A treatment is continued despite these subtle early changes, further symptoms may occur including red eye, lid edema, moderate epiphora, and scleral show. These changes may be classified as “moderate” with a grade of 2+ (Figure 1). If BTX-A is still continued in the face of these changes, advanced complications may occur including severe epiphora, pain, photophobia, ectropion, lower lid herniation, and corneal erosion. These are classified as “severe” changes with a grade of 3+ (Figure 1).

Figure 1.

The manifestations of dry eye syndrome with continued injections of BTX-A into the lateral rhytid regions are shown in this figure. One or more of these findings are commonly present simultaneously.

With worsening symptoms, patients generally seek medical attention and are often treated by their primary care physician for various conditions such as “dry eyes,” “blepharitis,” “eye allergy,” or are referred to an ophthalmologist. We have found that patients rarely return to their original surgeon for the above complaints and the correlation between BTX-A injection and dry-eye state, and thus a causal link is typically not suspected by patients or their primary care physician.

It is our contention that the aforementioned manifestations are due to botulinum neurotoxin's chemodenervation of the orbicularis oculi muscle that, in turn, leads to poor blink mechanism, lagophthalmos, and ectropion that may result in corneal dryness with the resulting symptoms of eye irritation, foreign body sensation, and epiphora. The etiology of epiphora is likely due to a combination of factors including dry eye syndrome causing reflex tearing, hypotonicity of the medial pretarsal fibers causing decreased outflow of tears, and malposition of the eyelids, causing impaired retention of tears. If BTX-A treatment is continued in the presence of these early symptoms, increased tearing with possible redness and lid edema may result that could potentially lead to corneal erosion and even ulceration as its most ominous manifestation (Figure 1).^2,3

Paradoxically, BTX-A has also been found useful in treating dry eye syndrome.^5,12 In these reports, BTX-A was injected into the periorbital area including the medial portion of the orbicularis muscle and not solely into the lateral canthal region, for the treatment of existing dry eye syndrome. The mechanism of action of BTX-A on lacrimal drainage in such instances has been postulated to involve a paralysis of the orbicularis oculi muscle acting on the canaliculi with a decreased compression of these structures as well as weakness of apposition of the puncta during blinking.¹² Counterintuitively however, the increase in tear collection from diminished punctal drainage is incapable of improving the symptoms of advanced dry eye syndrome and other forms of treatment are often necessary.^2–4

It has been suggested that the injection of BTX-A directly into the lacrimal gland may diminish states of hyperlacrimation as seen in Frey's syndrome or gustatory tearing, or in cases of lacrimal duct obstruction, by blocking the release of acetylcholine from presynaptic parasympathetic nerve fibers that innervate the gland, similar in mechanism to the injection of BTX-A in the treatment of palmar and axillary hyperhydrosis.^15–18 Therefore, one may theorize that a portion of BTX-A that is injected into the lateral canthal area could diffuse into the lacrimal gland and thus diminish tear production aggravating the dry-eye state and its manifestations.

In animal experiments, changes of contractile force in skeletal muscles of cats and rabbits were studied and showed changes in strength, muscle mass, and contractile ability after BTX-A injections.^19–21 Unfortunately none of these animal studies evaluated long-term adverse effects of repeated BTX-A injection on muscles. In clinical settings, there is clear evidence that permanent weakness or paralysis of facial muscles may result when facial muscles are denervated longer than 1.5 to 2 years as reported by Terziz and others.^22,23 For this reason, we may assume that continued injection of BTX-A over a period of 1.5 to 2 years may cause permanent weakness of the orbicularis muscles as has been observed in several of our patients.

Our current practice consists of grading and documenting any eye symptoms or findings prior to BTX-A injection as illustrated in Figure 1. In addition, we document the results of snap-back and distraction tests before any injection. The snap-back test is performed by pulling the lower lid inferiorly while patient looks straight ahead without blinking. Upon releasing, if the recoil is not immediate before the next blink, the snap-back test is positive and is documented in seconds. The test is considered mildly positive with a grade of 1+ if the lower lid returns back to the globe in 1 to 2 seconds, as moderate with a grade of 2+ if it returns in 2 to 4 seconds, and finally as severe with a grade of 3+ if it returns to the globe with the next blink. The snap-back test measures muscle tone and must not be confused with lower lid distraction test that measures lid laxity resulting primarily from the stretching of canthal ligaments.⁸ The distraction test is performed by pulling the lower lid forward gently away from the globe with the thumb and index fingers and is considered normal if the distance between globe and central lid margin is less than 2 mm. If it measures between 2 and 4 mm, it is considered mild with a 1+ grade. If it is between 4 and 6 mm, it is considered moderate with a 2+ grade. A distance greater than 6 mm is considered severe with a 3+ grade (Table 1).

Table 1.

Grading of snap-back and distraction tests.

Proposed classifications for snap-back and distraction tests for patients receiving BTX-A injection
Grade	Snap back test*	Distraction test**
1+ (mild)	1 to 2 seconds	<2 mm
2+ (moderate)	2 to 4 seconds	4 to 6 mm
3+ (severe)	next blink	>6 mm

^*Test accomplished by pulling the lower lid inferiorly while patient looks straight ahead and measuring the time it takes for the lower lid to return to globe.

^**Test accomplished by pulling the lower lid forward away from the globe with thumb and index fingers and measuring the distance between the globe and central lid margin.

By questioning the patient about any early symptoms such as eye irritation, foreign body sensation, or tearing that were not present previously and/or by noticing any change in snapback and distraction tests during the treatment course, we have been able to avoid advanced manifestations by temporarily discontinuing BTX-A injections into the lateral canthal rhytids. These early “mild” changes have been noted in approximately 5% of our patients undergoing injections of up to 10 Units of BTX-A into each lateral canthal region and all have reversed within approximately 3 to 6 months of observation. Prior to the use of this approach, we witnessed persistent moderate changes in approximately 1% of patients receiving BTX-A injections for longer than one year. Thus far no “severe” change has been observed by us.

In instances when the manifestations of dry-eye state (Figure 1 and Table 1) remain troublesome to the patient and do not reverse within one year of observation and conservative management, performing lateral musculoplasty of the lower eyelid similar to the techniques described by Fogli has been successful.²⁴ Typically, an anchor stitch of 5-0 absorbable monofilament is placed into the dense and supportive fibrous tissue of the lateral orbital rim at the level of the lateral canthal ligament and through the lateral aspect of the pretarsal orbicularis oculi muscle as well as the muscular portion of the lower eyelid's musculocutaneous flap (Figure 2). In cases of a prominent globe and negative vector, placement of the lateral canthal suture may be modified or the tension on the muscles diminished. If there is concomitant fat herniation of the lower lid possibly due to BTX-A injections²⁶ or from another cause, a fat-preserving hernia repair^27,28 or another technique may be utilized.

Figure 2.

Schematic drawing shows the placement of the lateral anchor suture for correction of persistent orbicularis oculi paresis.

Conclusion

Dry eye syndrome of varying severity may develop when BTX-A is repeatedly injected into the lateral canthal region for aesthetic correction of crow's feet. Early suspicion of this condition is suggested by subtle eye irritation, foreign body sensation, and epiphora. If BTX-A injections are continued, worsening of the manifestations may take place (Figure 1). These manifestations seem to be due to orbicularis oculi muscle weakness and may become worse and possibly persistent if BTX-A injection is not delayed or discontinued. Our clinical experience indicates that inquiry for the presence of any dry eye symptoms as well as routine snap-back and distraction tests prior to BTX-A injections help early detection of this condition and therefore we recommend their use. When conservative management of dry eye syndrome due to BTX-A injection over a period of 6 to 12 months fails, we have had success in resolving it by performing musculoplasty as shown in Figure 2.

Disclosure Statement

None of the authors identify any conflict of interest.