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Monopolar Radiofrequency Treatment of the Eyelids:

A Safety Evaluation
BRIAN S. BIESMAN, MD, FACS,AND KARL POPE, MSy

BACKGROUND Monopolar radiofrequency (RF) energy has been used to successfully accomplish non-
invasive skin tightening of the face, abdomen, and extremities. Owing to concerns about injury to the
eye itself, monopolar RF treatment of the eyelids has not been feasible.
OBJECTIVE The objective was to evaluate the safety of a novel 0.25-cm 2 ‘‘shallow’’ treatment tip for
noninvasive tightening of eyelid skin.
METHODS AND MATERIALS This was a tripartite study that began with an animal model to evaluate soft
tissue effects and temperature change at the ocular surface. Findings were then extrapolated to ex vivo
evaluation of human eyelids and ultimately to an in vivo human eyelid safety study.
RESULTS The animal studies demonstrated that the 0.25-cm 2 treatment tip could be used safely on
eyelids in conjunction with appropriate ocular protection. The ex vivo human eyelid studies confirmed
that, at typical treatment settings, the shallow treatment tip did not produce frank eyelid injury. The
in vivo human studies confirmed that, at the tested settings, the novel treatment tip did not injure
the eyelids or eyes.
CONCLUSION If used properly, the 0.25-cm 2 treatment tip can be safely used on human eyelids.
Karl Pope is an employee of Thermage, which supplied the treatment tips for the study. Dr Biesman is a
consultant for Thermage Inc.

A esthetic periorbital rejuvenation is one of the


most commonly sought after aesthetic goals.
Anatomic changes occurring in this region with
riorbital rejuvenation. The fact that botulinum toxin
injection has become the most popular aesthetic
procedure suggests that many patients are interested
aging include laxity of eyelid skin, ‘‘hypertrophic’’ in pursuing nonsurgical rejuvenation options. To
orbicularis oculi muscle, prominent orbital fat pads, date, such an option does not exist for tightening or
and even descent of the forehead, eyebrows, and rejuvenating eyelid skin.
midface. Patients typically interpret these anatomic
changes as making them look ‘‘old’’ or ‘‘tired.’’ Re- The benefits of radiofrequency (RF)-induced skin
juvenation of the periorbital region has traditionally tightening have been well recognized.1–4 A com-
been limited to surgery of the eyelids, forehead, or mercially available RF device (ThermaCool,
midface. In the early 1990s, botulinum toxin type A Thermage Inc., Hayward, CA) uses a 6-MHz RF
began to gain widespread popularity for modifying generator to capacitively couple energy through a
the orbicularis oculi muscle and, more recently, fill- monopolar treatment tip to produce volumetric
ing agents such as hyaluronic acid have been injected tissue heating. This heating leads to an immediate
into the periorbital region to camouflage the volume conformational change in dermal collagen, tighten-
deficit produced by descended midfacial structures. ing of the fibrous septae extending from the dermis
Because each of these techniques complements one to the subcutaneous tissue, and stimulation of
another, they all can play an important role in pe- dermal neocollagenesis (K. Pope, M. Levinson, and

Departments of Ophthalmology, Otolaryngology, and Dermatology, Vanderbilt University Medical Center, Nashville,
Tennessee; yThermage, Inc., Hayward, California

& 2007 by the American Society for Dermatologic Surgery, Inc.  Published by Blackwell Publishing 
ISSN: 1076-0512  Dermatol Surg 2007;33:794–801  DOI: 10.1111/j.1524-4725.2007.33172.x

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BIESMAN AND POPE

E. V. Ross, personal communication, February


2005). The ThermaCool has FDA clearance for skin
tightening of the face, neck, and body. To tighten the
skin in these regions, RF energy is delivered via dis-
posable treatment tips approximately 2 to 3 mm
beneath the skin’s surface. It follows from the ex-
perience in other anatomic regions that delivery of
RF energy to the eyelids may produce favorable
aesthetic outcomes. Owing to the thin nature of the Figure 2. Dose response: Effect of 0.25-cm2 treatment levels
eyelid, the use of the existing treatment tips on the on piglet eyelid skin. Numbers represent treatment level,
not fluence. Note that erythema persists more than 1 hour at
eyelids may put deeper structures in the eyelid or higher treatment levels.
even the eye itself at risk of injury. We therefore
sought to develop a new treatment tip with the
capability of delivering monopolar RF energy to the Appropriate institutional review board (IRB) ap-
eyelids in such a manner that favorable aesthetic proval was obtained and all animal care guidelines
outcomes could be achieved without posing a risk to were followed. General anesthesia was administered
the eye. To this end, a novel 0.25-cm2 (0.5  0.5-cm) to a farm piglet weighing approximately 15 kg. A
treatment tip for the ThermaCool device was devel- return pad was placed on the back, and the upper
oped by Thermage, Inc. (Figure 1). This tip was and lower eyelids were divided into multiple equal-
modeled to have a penetration depth of 1.2 mm, the sized sections with a surgical marker (Figure 2).
level at which the electric field drops to 1/e (B37%) Ophthalmic examination was performed with a
of the surface energy. The testing process for this tip hand-held slit lamp before the initiation of studies.
involved four distinct stages: animal testing, treat- A plastic corneoscleral protective lens was placed
ment of ex vivo human eyelid skin, treatment of in behind the eyelids, and each section of the eyelid was
vivo human eyelid skin immediately before surgical treated with RF energy at a different fluence. Initially
excision, and finally clinical efficacy. This article will a dose–response type of study was performed, de-
describe the first three stages of this testing process; livering single-pulse treatment over a wide range of
clinical efficacy studies will be described separately. energies from very low to extremely high. Fluences
used in this portion of the study ranged from 40 to
93 J/cm2 (10–23 J). On the animal’s opposite side,
Methods studies were performed to evaluate the clinical ef-
Phase I: Animal Study fects of multiple-pass treatment application and to
determine the peak temperature produced at the
A farm piglet model was selected for the relative
ocular surface with a plastic corneoscleral lens
similarity between piglet and human eyelids.
(Oculo-Plastik, Montreal, Canada) in place. The
latter studies involved the use of a custom-designed
corneoscleral lens with a thermocouple embedded in
the posterior aspect of the lens (Figure 3). The
thermocouple was connected to a computer that
measured temperature 1,000 times/second. Tem-
perature change was measured with single-pulse en-
ergy delivery over a range of fluences, after multiple
passes allowing for cooling between passes, and then
in a pulse-stacking manner at fluences high enough
Figure 1. 0.25-cm2 ‘‘shallow’’ treatment tip. to produce frank epidermal injury (Figures 4 and 5).

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Figure 3. Corneoscleral protective lens with embedded thermocouple in position (A) and before insertion (B).

The latter measurements were taken at settings well eyelid blepharoplasty were harvested. Immediately
above those expected to be used clinically without after the conclusion of the surgical case, the lids were
allowing time for the skin to cool between passes in prepared for treatment with the ThermaCool device
an effort to assess ocular risk under the most dire using the 0.25-cm2 treatment tip. To simulate an RF
conditions. Ophthalmic examination was repeated treatment on the eyelid, a rubber mold in the shape
with a hand-held slit lamp at the conclusion of the of the eye was made. This simulated the non-
treatment. Before euthanization, the animal cornea conducting surface of the corneoscleral lens that is
was treated directly with the ThermaCool device to used to protect the eye. To replicate the attachment
assess the outcome of a catastrophic clinical error of the eyelid to the rest of the body, a moistened
(Figure 6). Finally, the eyelids were harvested for towel was placed in a saline bath, draped over the
histopathologic evaluation, and the eyes were enu- rubber mold and under the lid. Aluminum foil was
cleated. Histopathologic analysis of the eyelid skin used to create a ‘‘return pad’’ that was, in turn,
and globe was performed using standard hematox- connected to the RF generator to complete the
ylin and eosin stains. circuit (Figure 7). The RF generator delivered 68 or
76 J/cm2, a fluence extrapolated from the piglet data,
Phase II: Ex Vivo Analysis of Human Eyelid Skin to treat the eyelids in a single pass without pulse

After obtaining IRB approval of the proposed pro-


tocol and informed consent from all patients,
10 eyelids of five patients undergoing routine upper

Figure 5. Thermocouple measurements taken at corneal


surface during two passes at a setting of 38.5. This is well
above energy setting that would be tolerated clinically.
Figure 4. Thermocouple measurements taken at corneal Pulses were delivered with a pulse-stacking technique to
surface during two passes at 35.5. Pulses were delivered simulate a ‘‘worst-case scenario.’’ Note that peak tempera-
without pulse staking. Note that peak temperature was well tures remain well below the ocular injury threshold even
below the injury threshold. under extreme conditions.

796 D E R M AT O L O G I C S U R G E RY
BIESMAN AND POPE

Figure 6. Enucleated eye demonstrating corneal stromal opacification in outline of ThermaCool treatment tip after delivery
of RF energy directly to the cornea.

overlap. Three eyelids were treated at 68 J/cm2, provided for use in other anatomic regions
6 eyelids were treated at 76 J/cm2, and 1 served as was applied liberally to the eyelids. Patients were
a control. The tissue was then placed in 10% treated with the ThermaCool device using the
formalin solution and processed for histopathologic 0.25-cm2 treatment tip at fluences ranging from
evaluation. 68 to 100 J/cm2. The fluence was increased until the
patients reported subjective perception of discomfort
Phase III: In Vivo Treatment of Human of 2 to 2.5 on a 0 to 4 scale. Up to five passes were
Eyelid Skin performed. Pulses were applied in a nonoverlapping
fashion and pulse stacking was avoided. The treated
After obtaining IRB approval of the proposed
skin was allowed to cool a full 2 minutes between
protocol and informed consent from all patients,
passes, and treatment was only delivered to skin
20 eyelids from 10 patients undergoing routine up-
scheduled for immediate excision. Neither topical,
per eyelid blepharoplasty and/or blepharoptosis re-
regional, nor systemic anesthetic agents were used
pair were selected to participate in this phase of the
before ThermaCool treatment. The patients were
study. A drop of 0.5% proparacaine solution was
then sedated with intravenous diprivan and local
placed in each eye, and a plastic corneoscleral pro-
anesthesia 2% lidocaine with epinephrine was in-
tective lens (Oculo-Plastik) was placed behind the
jected into the eyelids in standard fashion for the
eyelids. Ellipses were marked on the eyelids to de-
blepharoplasty. The ellipses of treated skin were
note the proposed area of skin removal. A return pad
harvested, and the planned procedure completed.
was applied to the abdomen, and the coupling fluid
The excised tissue was placed immediately into 10%
buffered formalin solution for histopathologic
analysis. A baseline ophthalmic examination was
performed before and after treatment.

Results

Phase I: Animal Study

Figure 7. Experimental design permitting evaluation of ex Application of single pulses at very low fluences
vivo human eyelid skin. produced no visible change in the eyelid appearance

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TABLE 1. The Histologic Findings at Different Energy Levels on Bovine Eyelids

Eyelid Joules J/cm2 Histology

Left
L1 10 40 No findings
L2 13 52 No findings
L3 14 57 No findings
L4 16 64 No findings
L5 17 69 No findings
L6 20 81 0–1 (minimal superficial dermal inflammation)
L7 22 89 2
L8 23 93 2 1 (larger subepidermal blister than L7)
L9 0 0 ControlFno findings
Right
R1 10 40 No findings
R2 13 53 No findings
R3 16 64 No findings
R4 19 76 No findings
R5 22 88 No findings
R6 23 92 No findings
R7 23 92 No findings
Positions 1–6 were on the upper lid; higher numbers were on the lower lids.

while delivery of high energy pulses produced nearly (coagulative necrosis), but this was not a consistent
immediate erythema and, in some cases at 92 J/cm2, finding even at fluences high enough to produce
blistering (Table 1; Figure 2). These treatment levels immediate epidermal injury.
are no longer available with this treatment tip. Ex-
trapolating from these data helped suggest the pa- Temperature change at the ocular surface was
rameters to be used in Phase II, treatment of ex vivo assessed during single-pulse application, during
human eyelid skin. These parameters were further delivery of multiple passes performed at 2-minute
refined by multiple-pass treatment of the opposite intervals, and while a pulse-stacking technique was
eyelids. When multiple-pulse techniques (allowing utilized. At low to moderate energy settings using
cooling time between passes and pulse stacking) single- or multiple-pass technique at moderate
were employed at moderate energy settings, little or energy settings as would typically be used clinically,
no clinical changes were apparent. Mild erythema the temperature rise at the corneal surface was small.
was intermittently noted after pulse stacking at To create a worst-case scenario, pulse stacking
moderate energy. No frank epidermal injury was was performed at energy levels high enough
noted with either technique at these lower energy to create immediate whitening and blistering of the
settings. Histopathologically, there was no evidence epidermis. Under these extreme conditions, the
of injury or thermal effect to the epidermis, dermis, temperature elevated with successive passes
or orbicularis oculi muscle at low to moderate en- but peaked at just over 461C. Attempts to drive
ergy settings. Only when the pulse energy was high the ocular surface temperature higher with the
enough to produce immediate frank epidermal injury ThermaCool device applied to the eyelids were
did histopathologic changes consistent with thermal unsuccessful. Finally, deliberate application
injury become apparent. At these settings, histo- of the treatment tip to the ocular surface at moderate
pathologic analysis revealed epidermal necrosis energy setting produced immediate corneal
without obvious dermal injury. Occasional dermal opacification in the shape and size of the treat-
sections were suggestive of early thermal change ment tip electrode.

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Figure 8. Ex vivo human eyelid skin treated at 76 J/cm2. At low power (100  , A) an area of slightly increased eosinophilia is
observed although the epidermis remains intact. Examination of the designated area under higher power (400  , B) reveals
changes that my be consistent with early coagulative necrosis.

Posttreatment ophthalmic examination of the piglet adjusted until subjective sensation of discomfort was
eyes, including evaluation with a portable slit lamp, rated 2.0 to 2.5 on a 0 to 4 scale. Mild erythema and
was unchanged from the initial baseline. There was slight edema were present after some treatments but
no evidence of thermal injury to the conjunctiva, there were no instances of crusting, blistering, or
cornea, or lens except as noted for direct treatment deeper thermal injuries. Of equal significance, when
to the cornea. the planned procedure was subsequently performed,
all eyelid structures including the orbicularis muscle,
Phase II: Ex Vivo Analysis of Human Eyelid Skin orbital septum, orbital fat, levator palpebrae super-
ioris muscle, Müller’s muscle, and tarsus were nor-
Clinical changes were not noted after treatment of
mal in appearance and integrity. All patients had an
the excised human eyelid skin. The epidermis re-
uneventful postoperative course without complica-
mained intact without whitening or discoloration.
tions. Because only a limited ellipse of upper eyelid
Histopathologic evaluation of the nine treated lids
skin was scheduled for excision, skin tightening was
revealed no change in six of nine lids. Limited re-
not assessed. Histopathologic analysis of all 20 eye-
gions of one lid treated at 68 J/cm2 and two lids
lids with hematoxylin and eosin staining failed to
treated at 76 J/cm2 demonstrated changes suggestive
demonstrate epidermal injury or dermal coagulative
of mild thermal injury (Figure 8). This change was
necrosis. With the exception of the anticipated
not felt to be clearly indicative of thermal injury
changes induced by routine upper eyelid surgery,
because it was not found consistently through the
the postoperative ophthalmic examination was un-
affected specimens and was absent in a majority of
changed relative to the baseline taken preoperatively.
specimens treated. An artifact of tissue processing or
handling could not be eliminated.
Discussion
Phase III: In Vivo Treatment of Human
Although the skin-tightening effects of monopolar
Eyelid Skin
RF energy have been well established, RF treatment
Because this represented the first in vivo eyelid of the eyelids has not been previously attempted. On
treatment, the question of patient tolerance was of account of the thin nature of the eyelid, it was felt
primary significance. Without exception, all treat- that heating the lids with a device that has an elec-
ments were well tolerated. Treatment settings were trical penetration depth of approximately 2.5 mm

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could put the eye in jeopardy. These concerns ori- surgery technique in which the corneal contour is
ginated from previous reports of the effects of RF steepened to reduce hyperopia. Although estimates
energy on both human and animal eyes. Unfortu- of corneal temperature change have previously
nately none of these prior studies compare directly to suggested peak temperatures of 65 to 701C, finite
the nature of the energy delivered with the Therma- element computer models suggest that actual tem-
Cool RF generator. Cataractous opacification of the peratures reached may exceed 1001C.13 Because
crystalline lens has been observed in experimental none of the patients treated in our study experienced
animals when one eye was exposed to a localized, ocular pain or developed a change in visual acuity or
very high RF field and the other eye was the unex- refractive error after RF treatment of the eyelids with
posed control. Results of these studies demonstrated a corneoscleral shield in place, it is reasonable to
that 2,450-MHz exposures for more than 30 minutes assume that the temperature at the ocular surface did
at power densities causing extremely high dose rates not rise high enough to induce changes in corneal
(4150 W/kg) and temperatures of greater than 411C topography. With direct application of the RF elec-
in or near the lens caused cataracts in the rabbit eye. trode to the piglet cornea, immediate thermal
Cataracts were not observed in the monkey eye ex- changes due to denaturation of collagen were ob-
posed to similar exposure conditions, however. Be- served clinically and were confirmed histologically14
cause the monkey head is similar in structure to the (Figure 8).
human head, the nonhuman primate study showed
that the incident power density levels causing catar- Our observation that there was no frank coagulative
acts in rabbits and other laboratory animals cannot necrosis in the dermis of either the animal or human
be directly extrapolated to primates including hu- eyelid tissue is consistent with observations made by
mans. It is reasonable to assume that prolonged ex- Zelickson and colleagues.1 These authors did not
posure of humans to RF energies that would produce observe morphologic changes using light microscopy
heating of the lens to greater than 411C would be between treated skin and controls. Studies by other
cataractogenic; however, such exposure would be authors in which clinically apparent skin tightening
expected to cause thermal injuries to other parts of has been produced have also demonstrated no ap-
the eye, particularly the conjunctiva and cornea.5 parent immediate changes in treated tissue at the
Such injuries were not observed in either our animal light microscopic level.15
model or in the in vivo human study. While retinal
and lenticular injuries have been reported in animal
Conclusion
models and in vitro studies of human ocular expos-
ure to microwave radiation, the dosage and/or This study represents the first evaluation of the 0.25-
duration of radiation in these scenarios does not cm2 ‘‘shallow’’ treatment tip intended for use on and
correlate with the brief exposure sustained during around the eyelids. The goals of this study were only
ThermaCool treatment of the eyelids.6–12 Further, to evaluate the safety of this device relative to the
over the range of fluences tested in our in vivo pro- eyelid skin, delicate structures within the eyelid, and
tocol, minimal discomfort was reported in the eye- the eye itself and to determine patient acceptance of
lids and no patient reported actual ocular pain. This this technique. From our data, we believe that the
suggests that temperature at the ocular surface did ThermaCool RF generator may be used safely on the
not rise above 38 to 391C, confirming our experi- eyelids in conjunction with the 0.25-cm2 treatment
mental data generated with the thermocouple in the tip and adequate ocular protection with a plastic
piglet model.5 With substantial heating of the cor- corneoscleral lens in place. Extrapolation to clinical
nea, thermal modification of the stromal collagen outcomes; recommended treatment algorithms; and
can result in refractive change. This trait is capital- combination with other treatment options such as
ized upon in RF conductive keratoplasty, a refractive botulinum toxin, fillers, surgery, or others cannot be

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BIESMAN AND POPE

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8. Chou CK, Guy AW, Borneman LE, et al. Chronic exposure of Address correspondence and reprint requests to: Brian S.
rabbits to 0.5 and 5 mW/cm2 CW microwave radiation. Bioelec- Biesman, MD, 345 23rd Avenue North, Suite 416, Nash-
tromagnetics 1983;4:63–77. ville, TN 37203, or e-mail: bbies@mindspring.com

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