A novel hybrid BonT‐A and hyaluronic acid cannula‐based technique for eyelid ptosis and periorbital rejuvenation

Eyelid ptosis is characterized by an inferior displacement of the upper eyelid when the eye assumes its primary position. Besides its aesthetic implications, ptosis can also adversely affect visual acuity.

option.In this setting, we describe herein a novel non-surgical minimally invasive technique for eyelid ptosis treatment with injection of Incobotulinum toxin A (IncoBonTA) delivered with cannula in the safest portion of the orbicularis oculi (OO) (upper portion of OO, up to the mid-pupillary line) and a hybrid mixture of IncoBonTA and a hyaluronic acid with moderate cross-linking mixed in the same syringe delivered with cannula in the upper-lateral orbicularis oculi.
The aim of this study was to evaluate the simultaneous administration of IncoBonTA and hyaluronic acid effect in eyelid ptosis and ocular rejuvenation.

| Case report
A 40-year-old female with a complaint of a "tired look", with a personal history of botulinum toxin treatment for the upper face third

| Technique
To deliver a safe treatment, a comprehensive knowledge of the periorbicular anatomy and eyelid stratigraphy is crucial.The eyelid can be divided into 5 sections: skin, orbicularis oculi, orbital septum, eyelid retractor muscles, tarsal plates, and conjunctiva. 8The OO is a sphincter muscle located just underneath the skin of the eyelid and is divided into two sections, the orbital (over the bony orbital margins) and palpebral sections.The palpebral section is further subdivided into the preseptal and pretarsal sections. 9The marginal portion of the palpebral OO adjacent to the eyelid margin is known as the muscle of Riolan.The orbicularis oculi muscle closes the eyelids and assists in pumping the tears from the eye into the nasolacrimal duct system.It has been postulated that different portions of the OO may have different functions.For instance, the orbital portion would be mostly involved in forceful and sustained eye closure, the pre-septal portion closes the eyelid during a blink, and the pre-tarsal orbicularis would be more involved in the involuntary blink closure of the eye and keeping the eyelids closed during sleep. 10,11ing between the orbicularis muscle and the orbital septumlevator aponeurosis fascial complex is an avascular fascial plane composed of loose areolar tissue, below which there is the orbital septum (OS), a fibrous conjunctive tissue membrane that separates the orbital fat pads and deep orbital structures from the eyelid itself. 8The OS originates from the arcus marginalis, a line of periosteal condensation, along the superior and inferior orbital margins.The inferior aspect of the orbital septum merges into the anterior surface of the levator aponeurosis (LA). 8e main upper eyelid elevator muscle is the levator palpebrae superioris (LPS), 12 whereas other muscles involved in eyelid elevation include Muller's muscle, an accessory muscle that contributes with 1-2 mm of eyelid elevation 13 and the frontalis.The LPS originates from the sphenoid bone, broadens as it traverses the orbit, and becomes a fibrous aponeurosis that merges with the lower part of the orbital septum, extending downwards into the lid and inserting on the anterior aspect of the tarsus. 14LPS may have anatomic variations especially related to accessory muscle slips that connect the LPS to adjacent structures.The most relevant variations of the latter include those related to the lacrimal gland, the superior oblique muscle's trochlea, and the orbit's lateral wall. 13,15

| Inclusion criteria
Patients lacking surgical indications for blepharoplasty.

Individuals diagnosed with ptosis of aponeurotic classification.
Subjects presenting with mild to moderate ptosis.

| Exclusion criteria
Individuals with a history of blepharoplasty.
Patients diagnosed with myasthenia gravis or other antecedent neuromuscular disorders.
Subjects with infection present at the proposed injection site.

| Treatment area selection
The first step in this technique is the proper orbital rim circumference delimitation by simple palpation (Figure 1, white line).Then, a second line 1 cm lateral from the first line in the lateral orbital area is drawn.After that, a third line is drawn at 1 cm above the first line, in the mid-pupillary line.Finally, an ellipse is constructed by joining these two latter lines, following the design of the first line to delimit the area of the OO to be treated (Figure 1).It is paramount to maintain the 1 cm safety margin outside the first marking.
A vial of 100 IU Incobotulinum toxin (IncoBonTA; Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany) was diluted with 2 mL of saline solution.From the latter solution, 20 U of IncoBonTA is aspirated with a 1 mL syringe.From one syringe of hyaluronic acid (1 mL; CPM-HA; Belotero Balance®; Cohesive poly-densified matrix hyaluronic acid; Merz Pharmaceuticals GmbH, Frankfurt, Germany), 0.2 mL is aspirated into a 3 mL syringe.Using a female transfer adaptor products are mixed thoroughly, with at least 10 passes between syringes to ensure product homogeneity and a final volume of 0.6 mL.
From an entry point 1 cm above the lateral canthus (Figure 2A), inside the marked area, a 25Gx50mm cannula is inserted in the subdermal plane (when lifted, the cannula can be easily observed; Figure 2B).The cannula tip should be directed inferiorly to the lateral canthus (Figure 2B) and 0.4 mL per side of the hybrid solution is retro-injected in the lateral portion of the OO (Figure 3).Massage is performed thereafter.
Using the same entry point, in the superior portion of the OO, inside the delimited area, a 25Gx50mm cannula is advanced in the subdermal plane until the mid-pupillary line, and 5 U of IncoBonTA is retro-injected per side (Figure 4).

F I G U R E 1
Treatment area delimitation.Palpate and draw the circumference of the orbital rim (1).In the lateral orbital area, draw a second line, 1 cm from the first line (2).In the mid-pupillary line, draw a third line 1 cm above the first line (3).Connect the second and third markings (4) following the design of the first line to delimit the area of the OO to be treated.the pre-tarsal portion of the orbicularis oculi, 10 although it is not devoid of risks.This latter technique has been associated with a risk of ptosis (reported rate of approximately 0.5%-1%) 10,16 since in this area, the aponeurosis of the LPS and its fibers superficialize.
Moreover, considering that the pre-tarsal portion of the orbicularis is involved in keeping the eyelids closed during sleep, another possible side effect is related to eye dryness and its possible consequences (keratitis, ulcers).In the current technique, we prefer to approach the OO at its upper lateral portion since the eye globe is protected by the orbital bone, whereas in the pre-tarsal area, the eye globe is more exposed to perforation with a needle, leading to a higher risk of EP.Moreover, with the cannula, the injection is more comfortable for the patient since instead of multiple punctures, we use a single entry-point.
Treatment of other areas close to the eye may yield undesirable EP, in 5.4% of glabellar treatments with OnabotulinumToxinA (ONABonTA), 17 and 3% with AbobotulinumToxinA (ABOBonTA). 18ter deep injections of methylene blue in the corrugator supercilia in a single cadaver study, it was hypothesized that the toxin might reach the LPS muscle as it traverses the pre-periosteal plane or along tributaries of the superior ophthalmic vein, which travels along the LPS for part of its course. 19Nonetheless, it is still unclear if the spread of toxin through the orbital septum is the only way that BoNTA can access the LPS muscle since the OS constitutes a true anatomic barrier attached to the orbital ridge following a continuous fibrous junction.However, it does present a few weak points (i.e., supratrochlear, supraorbital, and lacrimal pedicles) that could allow for the unintended spread of toxin from the brow area to the intraorbital content. 20Anatomic variations in the exit point of the supraorbital neurovascular pedicle occur in 26% of the patients, providing a shorter route for BoNTA to travel, and thus making patients with this variant more prone to EP.In the current technique described herein, the OO is approached superiorly, up to the mid-pupillary line, since the neurovascular pedicles that cross the orbital septum are located medially to this line. 8Furthermore, the use of a cannula, instead of a needle allows a more superficial injection, also avoiding the risk of perforating the orbital septum unintentionally.Moreover, it is vital to consider that palpebral ptosis may require repetition of treatment in the long term.[23] For the periorbital area, since the effect of the BonTA is transient, the addition of an HA with optimal tissue integration for intradermal injection improves the treatment of the periorbital fine wrinkles, 24 aiming for long-term results, since HAB has been shown to improve skin quality and firmness. 25

| CON CLUS ION
This is a preliminary study, with a novel technique for eyelid ptosis treatment, based on injection of IncoBonTA delivered with the cannula in the safest portion of the orbicularis oculi (upper portion of OO, up to the mid-pupillary line) and a hybrid mixture of IncoBonTA and CPM-HA in the same syringe delivered with cannula in the upper lateral portion of the OO.Further studies are needed to corroborate the results.
for 4 years, and last botulinum toxin application 8 months before this evaluation.The patient refers to suffering occasional classic migraine attacks (2-3 crysis/year) treated with nonsteroidal antiinflammatory drugs (NSAIDs).No other relevant medical history or concomitant medications were registered.At physical examination, bilateral upper eyelid ptosis was diagnosed by abnormal Margin-reflex distance 1 (MRD1; distance between the central corneal light reflex and upper eyelid margin with eyes in primary position; 2 mm for the right eye and 3 mm for left eye), high palpebral crease height (distance between the upper eyelid margin and upper eyelid crease; normal range in women 9-11 mm) of 12 mm in both eyes, deep upper lid sulcus in both eyes, phenylephrine test was positive (sympathomimetic agents test the function of Muller's muscle) with the improvement of MRD1 for botheyes.The Hirschberg test was normal as well as the function of LPS, fatigue test to exclude myasthenia gravis.Based on the clinical findings, the hypothesis was aponeurotic palpebral ptosis.1,7

F I G U R E 2
Entry point and plane of treatment.(A) Entry point above the lateral canthus.(B) Insert the cannula in the subdermal plane.When in the correct plane, the cannula can be easily observed.F I G U R E 3 Hybrid solution injection.(A) Fanning retrograde injection technique.(B) Post-injection massage.Aperture and closure of the eyelid rest upon a balance between elevator muscles, mainly LPS, and antagonists, such as orbicularis oculi.For non-surgical, minimally invasive EP treatment with BotulinumtoxinA (BonTA), the objective would be to chemodenervate the orbicularis oculi, shifting the balance in favor of the elevators.The use of BonTA injection for EP has been previously described, especially the injection of micro doses of BonTA into

F I G U R E 4
Eyelid ptosis treatment.From the same entry point, advance the cannula in the subdermal plane until the midpupillary line.Retroinjection of 5 U/side of IncoBonTA should be performed.The exclamation mark signifies the mid-pupillary line as the furthest point of advancement with the cannula.Beyond this point, the emergence of the supraorbital and supratrochlear neurovascular bundles can be found, representing permeability points of the septum.F I G U R E 5 40-year-old female before (A, C, E) and after 15 days of treatment (B, D, F).Note the correction of droopy eyes, secondary improvement of palpebral sulcus depth (B), and aesthetic improvement of the periorbital area (D, F).