Botulinum toxin-induced blepharoptosis: Anatomy, etiology, prevention, and therapeutic options

Abstract

Background: Botulinum toxin A (BoNT-A) has grown tremendously in aesthetic dermatology since 2002 when the United States Food and Drug Administration (FDA) first approved its use for treating moderate-to-severe glabellar lines. Blepharoptosis, due to local spread of toxin, is a reported side effect of BoNT-A which, although rare, more frequently occurs among inexperienced practitioners.

Objectives: The purpose of this review is to highlight the causes and management of eyelid ptosis secondary to BoNT-A administration including new anatomic pathways for BoNT-A spread from the brow area to the levator palpebrae superioris muscle.

Methods: A literature search was conducted using electronic databases (PubMed, Science Direct, MEDLINE, Embase, CINAHL, EBSCO) regarding eyelid anatomy and the underlying pathogenesis, presentation, prevention, and treatment of eyelid ptosis secondary to BoNT-A. Anatomic dissection has been performed to assess the role of neurovascular pedicles and supraorbital foramen anatomic variations.

Results: Blepharoptosis occurs due to weakness of the levator palpebrae superioris muscle. Mean onset is 3-14 days after injection and eventually self-resolves after the paralytic effect of BoNT-A wanes. Administration of medications, such as oxymetazoline hydrochloride or apraclonidine hydrochloride eye drops, anticholinesterase agents, or transdermal BoNT-A injections to the pre-tarsal orbicularis, can at least partially reverse eyelid ptosis. Anatomic study shows that a supraorbital foramen may be present in some patients and constitutes a shortcut from the brow area directly into the orbital roof, following the supraorbital neurovascular pedicle.

Conclusion: Providers should understand the anatomy and be aware of the causes and treatment for blepharoptosis when injecting BoNT-A for the reduction of facial wrinkles. Thorough anatomic knowledge of the supraorbital area and orbital roof is paramount to preventing incorrect injection into "danger zones," which increase the risk of eyelid ptosis.

Keywords: anatomy; blepharoptosis; botulinum toxin; eyelid; ptosis; review.

FIGURE 1

Facial muscle anatomy

FIGURE 2

Anatomic skull specimen showing anatomic variations of the supraorbital pedicle: supraorbital foramen (A) or supraorbital notch (B)

FIGURE 3

(A, B) Anatomic dissection of the superior periorbital area. Anatomic location of the brow above the superior orbital ridge is seen here (Figure 3A). Skin elevation of the supraperiosteal layer (Figure 3B) with the forehead flap pulled downward, showing the bony insertion of the head of the Corrugator Supercilii muscle on the glabella, just below the superciliaris bony eminence of the frontal bone. This bony eminence is always palpable and constitutes an important landmark for the injection of BoNT‐A in the proper place that is between the supero‐medial orbital angle and the frontal eminence. Lateral to the corrugator muscle insertion, two neurovascular pedicles are visible: medially the supratrochlear and laterally the supraorbital. In this case, the supraorbital neurovascular pedicle is passing through frontal bony foramen. As shown here, a BoNT‐A injection performed close to the mid‐brow area may provide toxin direct access through the supraorbital foramen to the intraorbital bony roof

FIGURE 4

(A, B) Anatomic dissection of the superior periorbital area (Part II). After sub‐periosteal elevation, the frontal flap is pulled downward, showing the supraorbital pedicles and the superior orbital ridge. It is important to note how the supraorbital pedicle can exit the orbit through two different pathways: the supraorbital foramen on the left side (A) and the supraorbital notch on the opposite side (B). Hence, the spread of BoNT‐A may be different in the same patient depending on this anatomic bony variation: longer distance on the “notch side” and shortcut on the “foramen side.” This demonstrates significant differences in intraorbital spread of toxin depending on anatomic variation

FIGURE 5

Orbital septum anatomy. Left side, front view. The skin and orbicularis oculi muscle have been resected to show the underlying orbital septum; the neurovascular pedicles have been resected together with the periorbital soft tissues. The superior orbital septum is attached onto the orbital ridge following a continuous fibrous junction. The supratrochlear, supraorbital, and lacrimal pedicles are the only passages allowing for toxin spread from the brow area to the intraorbital content. The biggest neurovascular pedicle is the supraorbital pedicle which connects to the LPS muscle

FIGURE 6

Eyelid anatomy

FIGURE 7

Orbital roof, superior view. The forceps are medially pulling on the LPS muscle. Whitnall's ligament is shown as a white transversal structure that corresponds to the junction between the LPS muscle and its aponeurosis. The rectus superior muscle is visible just underneath the LPS muscle

FIGURE 8

Measurement of marginal reflex distance 1 (red), marginal reflex distance 2 (blue), and palpebral fissure (green)

FIGURE 9

(A, B) Anatomic dissection of left orbit. The superior bony framework has been resected together with the orbital septum and the fat compartments to show the LPS muscle, Whitnall's ligament, and the LPS aponeurosis that extends from Whitnall's ligament to the upper lid tarsus and skin close to the eyelashes. LPS muscle has been released from its posterior insertion and is pulled upward and spreads transversally into a fan shape. In Figure 8B, magnified on the LPS aponeurosis, Whitnall's ligament is pulled with two forceps. By transparency through the LPS aponeurosis, Müller's STM is showing an orange color with longitudinal muscular fibers

FIGURE 10

Patient presenting with eyelid ptosis after BoNT‐A injection for left hemifacial spasm. Visit 2: 17 days post‐BoNT‐A injection; (A) patient looking frontward; (B) looking upward; (C) looking downward; and (D) frowning. Visit 2: 17 days post‐BoNT‐A injection; 30 min post‐apraclonidine 0.5% ocular drops. Visit 3: 30 days post‐BoNT‐A injection; the patient feels improved but not fully resolved. Visit 4: 45 days post‐BoNT‐A injection; the patient returned to quasi‐normal life

FIGURE 11

(A, B) Coronal anatomic cross section of the orbital meridian and lacrimal gland. Oculomotor muscles surround the orbit and insert at the sclera. The lacrimal gland is located in the orbital superior lateral angle. In the superior orbital compartment, one can recognize the ramus nervus supratrochlearis and supraorbitalis of the nervus frontalis, the musculus levator palpebrae superioris, musculus rectus superior, ligamentum transversum superior (Whitnall's ligament), and glandula lacrimalis

FIGURE 12

(A, B) Anatomic dissection of the orbital roof. Left orbit, superior view. (A): The bony roof and the periosteum have been resected. The first anatomic structure located immediately under the orbital roof is the frontalis nerve that divides into supraorbitalis and supratrochlearis. Located immediately underneath the frontalis nerve, the levator palpebrae superioris lies just above the rectus superior muscle. (B): The frontalis nerve has been divided to show the underlying muscles. The other visible muscle is the superior oblique muscle, oriented medially