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January 2025

Quantitative Assessment Of Facial Ptosis In Face Transplantation

Sam Boroumand

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Boroumand, Sam, "Quantitative Assessment Of Facial Ptosis In Face Transplantation" (2025). Yale
Medicine Thesis Digital Library. 4300.
https://elischolar.library.yale.edu/ymtdl/4300

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 Yale School of Medicine

Doctor of Medicine-Master of Health Sciences (MD-MHS) Thesis

Quantitative Assessment of Facial Ptosis in Face Transplantation

By: Sam Boroumand

Thesis Mentor:

Bohdan Pomahac, MD1

Thesis Committee:

Michael Alperovich, MD, MSc1

David J. Leffell, MDCM2

1
Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of

Medicine, New Haven, CT

2
Section of Dermatologic Surgery and Cutaneous Oncology, Department of Dermatology,

Yale School of Medicine, New Haven, CT

Department of Surgery- Division of Plastic and Reconstructive Surgery

330 Cedar Street (Boardman Building)

New Haven, CT 06510

1
Abstract

As a transformative surgical procedure, face transplantation restores form and

function to patients with severe facial disfigurements, yet the long-term aging dynamics

of transplanted tissues remain poorly characterized. This study aimed to investigate the

progression of facial ptosis in transplanted facial allografts over time, addressing a

critical gap in the understanding of long-term outcomes following face transplantation.

Specific aims include quantifying ptosis progression using cephalometric measurements,

identifying regional variations in the degree of ptosis across the face, and comparing

changes between face transplant recipients and a non-face transplanted control cohort to

contextualize findings.

To assess these aims, standardized frontal headshots of nine face transplant

recipients were analyzed at three time points: T0 (1 year post-transplantation), T1 (3

years post-transplantation), and T2 (most recent follow-up photograph available post-

transplantation, median follow-up of cohort: 9 years). Utilizing ImageJ software, ten

independent cephalometric measurements adapted from the literature were employed to

assess facial ptosis at each timepoint in this patient cohort. These metrics include

eyebrow peak angle (bilateral), eyebrow tail angle (bilateral), vertical eyelid-iris ratio

(bilateral), lateral canthus-oral-nasal angle (bilateral), bigonial-bizygomatic ratio and

ergotrid length-upper lip ratio. These same measurements were performed on a group of

ten non-face transplant human subjects at two timepoints, T1 and T2, with a median time

interval of 78 years between them. Various descriptive analysis and non-parametric

statistical tests were utilized for evaluating the results.

2
 The results demonstrated significant changes between median values at T1 and T2

of the face transplant cohort when examining the left eyebrow peak angle (T1: 28.54° vs

T2: 20.98°, p=0.0239), left eyebrow tail angle (T1: 7.01° vs T2: 15.32°, p=0.0085), right

eyebrow tail angle (T1: 6.30° vs T2: 15.53°, p=0.0008), left lateral canthus-oral-nasal

angle (T1: 42.80° vs T2: 37.72°, p<0.0001), bigonial-bizygomatic ratio (T1: 0.87 vs T2:

0.91, p=0.0007), and ergotrid length-upper lip ratio (T1: 0.77 vs T2: 0.83, p=0.0007).

There was no significant difference noted between median values at T1 and T2 when

examining the right eyebrow peak angle (T1: 27.79° vs T2: 20.59°, p=0.1821), left

vertical eyelid-iris ratio (T1: 0.65 vs T2: 0.62, p=0.1944) and the right lateral canthus-

oral-nasal angle (T1: 42.68° vs T2: 37.11°, p=0.0689). Across all facial ptosis metrics

evaluated in the upper, middle, and lower face there was no significant difference

between T0 and T1 timepoints (p>0.05). Sub-analysis of the cohort across applicable

facial ptosis metrics between patients with bony components included in their allograft

versus myocutaneous only allograft highlighted in overall trend toward greater facial

ptosis in myocutaneous only allografts. When examining the non-face transplant cohort,

all facial ptosis metrics demonstrated significant changes between the two timepoints. A

comparison of the median change in various facial ptosis metrics from T1 to T2 of the

face transplant cohort compared to the non-face transplant human subjects demonstrated

no significant difference across all facial ptosis metrics evaluated except for the ergotrid

length-upper lip ratio which demonstrated significantly greater ptosis in the non-face

transplant cohort (0.14 vs 0.07; p=0.0220).

This study is the first to provide a direct quantification of the degree of facial

ptosis seen in face transplant recipients over time. Ultimately, the findings underscore the

3
critical need for ongoing surveillance and periodic revision procedures in face transplant

recipients to maintain functional and aesthetic outcomes over the long term. While early

revisions mitigate ptosis during the initial years post-transplantation, significant ptosis

observed at longer follow-up intervals demonstrates the limitations of these interventions

in addressing long-term tissue laxity. Preliminary findings here suggest that incorporating

skeletal subunits into facial allografts may provide biomechanical advantages by

preserving ligamentous support and reducing ptosis. Additionally, the findings of this

research contribute to the growing understanding of facial allograft aging and offers a

comparative framework against natural facial aging. The comparative ptosis progression

across a median 6-year time interval of face transplant patients equalizing to a median 78-

year time interval of non-face transplant human subjects underscores the potentially

accelerated aging dynamics of facial allografts as they relate to facial ptosis. Collectively,

these findings provide a foundation for optimizing surgical techniques, improving long-

term care strategies, and expanding the utility of facial ptosis metrics in reconstructive

and rehabilitative medicine.

4
Acknowledgements

The primary author would like to thank Dr. Bohdan Pomahac for his continued

guidance, support, and encouragement over the years. It has been an absolute privilege to

work and learn alongside him as not only a global leader in the field of face

transplantation and all things VCA but as a charismatic mentor and skilled plastic and

reconstructive surgeon. The primary author additionally would like to thank Dr. David J.

Leffell and Dr. Michael Alperovich for their time and commitment as part of the thesis

committee and for their valued wisdom and feedback that helped bring this final version

of the thesis to fruition.

The research underlying this thesis was made possible by financial support from

the National Institute on Aging of the National Institutes of Health and the Jane

Danowski Weiss Family Foundation Fellowship at Yale University School of Medicine in

conjunction with the Office of Student Research.

5
Table of Contents

Title Page……………………………………………………………………………….…1

Abstract……………………………………………………………………………………2

Acknowledgements………………………………………………………………………..5

Introduction………………………………………………………………………………..7

Statement of Purpose……………………………….……………………………...…......17

Methods………………………………………………..……………………………..…..18

I. Student Contribution………………………….…………………………….....18

II. Ethics Statement ………………………………………………………………18

III. Human Subjects Research…………….……………………….………………18

IV. Laboratory Animals……………………………………………………….…..19

V. Methods Description ………………………………………………….………19

VI. Statistical Methods… …………………………………………………………24

Results……………………………………………………………………………………25

Discussion……………………………………………………………………………..…43

Challenges & Limitations………………………………………………………………...53

Conclusion ………………………………………………………………………….……55

Dissemination ……………………………………………………………………………57

References………………………………………………………………………..………58

6
Introduction

Overview

Face transplantation, a groundbreaking form of reconstructive surgery in which a

donor face is transplanted onto a recipient who has suffered catastrophic facial

disfigurement, represents one of the most significant surgical innovations to date.1,2 This

approach is designed to restore not only a semblance of normal appearance but also

critical functions such as blinking, breathing, speech articulation, sensation, and facial

expression, all of which profoundly impact a patient’s quality of life and psychosocial

well-being.3-5 The very first face transplant was performed in 2005 in Amiens, France.6 A

surgical team successfully transplanted the lower face of a brain-dead donor onto a

patient who sustained a severe dog bite injury resulting in significant facial soft tissue

avulsion of the lips, nose, and cheek. This landmark event received worldwide attention

and generated intense debate on the ethical, immunological, and surgical considerations

of the procedure. The groundbreaking surgery demonstrated that it was possible to re-

establish a well-vascularized composite facial structure, leading to functional

reinnervation and a remarkable improvement in both appearance and quality of life. In

the past two decades since this revolutionary procedure, multiple centers around the

world—across primarily North America, Europe, and Asia—have performed face

transplantation (both partial and full) marking over 50 operations to date.7

Face transplantation is classified as a type of vascularized composite

allotransplantation (VCA), a category of transplantation that involves the transfer of

multiple tissues (skin, muscle, bone, mucosa, etc.) as a single functional unit from a

donor to a recipient.8-10 Other forms of VCA include hand and upper extremity

7
transplants, abdominal wall transplants, laryngeal transplants, and even more recent

applications such as uterine and penile transplants.11-13 The rationale behind VCA is that

when tissues are transplanted together as a composite unit, they can reestablish

anatomical form and function that would be exceedingly difficult, if not impossible, to

achieve using conventional autologous tissue transfer or prosthetic devices.14-16

Indications and Patient Selection

The indications for face transplantation typically include severe facial deformities

that have arisen from trauma (blast injuries, severe burns, animal attacks), congenital

anomalies, or disease processes such as advanced neurofibromatosis or massive

oncologic resections that have left patients with disabling deficits.1,17,18 In these cases,

traditional reconstructive options—often multiple staged free flaps or prosthetic

implants—cannot restore intricate facial structures and delicate soft tissues with sufficient

precision or functional outcome. The rationale for performing a face transplant hinges not

only on improving the patient’s cosmetic appearance but more critically on restoring

essential functions such as eyelid closure to protect vision, oral competence for speech

and nutrition, and an expressive facial appearance that allows for nonverbal

communication and social reintegration.19,20 The ultimate therapeutic goal is holistic

rehabilitation, transforming an individual’s life trajectory and enabling a return to a more

normal pattern of social interaction and self-perception.2,21

Appropriate patient selection is integral to the long-term success of face

transplantation and involves a comprehensive evaluation of both medical and

psychosocial factors.22 Candidates must demonstrate that their defect is too extensive to

8
be appropriately addressed with conventional reconstructive options. They must also have

a relatively stable medical profile, with no uncontrolled comorbidities, infections, or

cancers that would contraindicate them to the intensive immunosuppression regimen

required.1,23,24 Detailed immunological screening, including human leukocyte antigen

(HLA) matching, crossmatching, and panel-reactive antibody testing, helps identify a

compatible donor and minimize acute and chronic rejection risks.25,26 Psychosocial

evaluation is equally important. Patients must have realistic expectations following the

outcome of the procedure, stable psychological health, robust social support systems, and

a thorough understanding of the lifelong commitment to immunosuppressive therapy and

follow-up care.1,20,23

Surgical Planning and Approach

The surgical planning process for face transplantation is complex and highly

individualized. Preoperative planning involves advanced imaging modalities such as

high-resolution CT angiography and MR angiography to map the recipient’s vascular

anatomy and evaluate recipient vessels for microvascular anastomoses.27-29 Three-

dimensional (3D) modeling and virtual surgical planning allow for precise definition of

bony cuts, soft tissue restoration, and optimal graft design.30 Donor selection and

procurement planning require coordination with organ procurement organizations and

strict adherence to protocols ensuring proper donor consent, infection screening, and

tissue compatibility testing.31 Preoperative simulations, including cadaveric rehearsals,

are frequently utilized to refine surgical strategy and improve team coordination.25,32,33

9
 Surgical techniques in face transplantation build upon principles of microsurgery

and craniofacial reconstruction, demanding meticulous attention to vascular anastomoses

and neural coaptations. Typically, the procedure begins with a two-team approach: one

team prepares the recipient’s defect for allograft inset, and another harvests the donor’s

composite facial allograft. By definition the composite facial allograft consists of skin,

subcutaneous tissue, mucosa, muscle, fascia, nerves, and potentially bony segments

(mandibular/maxillary components).23,34 The vascular anastomoses, usually performed

under an operating microscope, commonly involve end-to-end connections between the

external carotid branches (e.g., facial artery) of the donor and recipient.1,35 Rigid fixation

plates and screws are used to secure the bony framework when underlying bone is

included in the composite allograft. Neural coaptations—facial nerve branches for motor

function and trigeminal nerve branches for sensation—are carefully performed to

facilitate eventual reinnervation and functional recovery.27

Post-Operative Outcomes

Face transplantation has demonstrated a wide range of positive outcomes in terms

of functional/motor recovery, sensory reinnervation, aesthetic improvement, and

psychosocial rehabilitation. Functional restoration typically includes improvements in

oral competence, eyelid closure to protect the cornea, and the capacity to produce facial

expressions.4,36 A complete review by Fischer et al. examined the functional facial

abilities of 29 face transplant patients post-operatively.37 They specifically examined five

functionalities: ability to smell, breathe, eat, speak, grimace, alongside overall facial

sensation. Prior to face transplantation, patients had significant disability in the majority

10
of these functionalities. However, post-transplantation it was reported that the ability to

smell, eat, and feel were enhanced in 100% of cases, while the ability to breathe, speak,

and demonstrate facial expressions was improved in 93%, 71%, and 76% of cases,

respectively, with follow-up times ranging 1-5 years. Other studies have reported similar

positive trends, including a recent retrospective 10 year follow-up of nine face transplant

patients by Huelsboemer et al. that additionally reported stable or increasing speech

intelligibility in the majority of patients (55.6%).5,17,36,38 Of note, it has been hypothesized

that the level (more proximal versus distal) at which facial nerve coaptations are

performed between the recipient and donor allograft may impact the degree of motor

function restoration.35,39 While examining facial expression intensities with visual

analysis software, Dorante et al. identified that across a cohort of eight face transplant

patients, those that had more distal facial nerve branch coaptations benefited from a 14%

greater restoration of motor function relative to those who had more proximal facial

nerve trunk coaptations.40

The degree of facial sensation of face transplant patients has also seen positive

impacts following transplantation. A 5 year review of six face transplant patients by

Tasigiorgos et al. noted significant improvement in the return of sensory function

especially within the first year post-transplantation.4 This improvement was captured

across all three assessment modalities utilized including two-point discrimination

(+3.94% per month), hot and cold discrimination (+5.68% per month), and Weinstein

Enhanced Sensory Test (WEST) monofilament sensation (+4.98% per month). Aesthetic

outcomes have been equally as promising as highlighted in Figure 1. Following their

procedure, patients have reported increased satisfaction with their self-appearance,

11
increased self-confidence, and greater comfortability with integrating back into society

with their new appearance.41,42 Important to note that these aesthetic gains are not purely

cosmetic; improved facial harmony and expressiveness enable recipients to engage more

confidently in social interactions, often resulting in a perceived normalization of

appearance.43,44

Figure 1. Aesthetic outcomes following face transplantation. Pre (A) and post (B)-
operative facial headshots of six patients having undergone face transplantation. Patients
I-IV underwent full face transplantations while patients V and VI underwent partial face
transplantations. Reproduced with permission from Tasigiorgos S, Kollar B, Turk M, et
al. Five-Year Follow-up after Face Transplantation. N Engl J Med. 2019;380(26):2579-
2581. Copyright Massachusetts Medical Society.

Beyond functional and aesthetic recovery, one of the most meaningful

achievements of face transplantation is the social reintegration of patients who have often

endured years of social stigmatization, isolation, and psychological distress. Studies have

demonstrated marked improvements in self-esteem, body image, and quality of life

12
following face transplantation.43,45 In examining patients’ self-reported quality of life as

evaluated on the EuroQol Group–5 Dimensions Visual Analogue Scale (EQ-5D VAS),

Tasigiorgos et al. noted a trend toward improvement between baseline and five-year

follow-up among a cohort of six patients, while also noting a trending decrease in the

Center for Epidemiologic Studies Depression Scale (CES-D) score, indicating lower risk

of a clinical depression episode at five-year follow-up.4 Of note, age of recipient at time

of transplantation has been identified as a significant factor for dictating psychosocial

well-being of patients as Huelsboemer et al. identified that older recipient age strongly

correlated with higher levels of mental health and propensity to seek out comfort and

advice from support systems.21 These psychosocial impacts reinforce the notion that face

transplantation is not solely a reconstructive procedure but rather a profoundly life-

changing intervention that addresses both the physical and emotional dimensions of facial

identity.

Challenges

Despite the incredible outcomes and potential of the field, face transplantation

faces a host of challenges that influence its feasibility, safety, and long-term success. One

of the most critical issues is the requirement for lifelong immunosuppression to prevent

significant graft rejection.26,46 The majority of immunosuppression protocols utilized for

VCA have been adapted from solid organ transplantation models.47,48 As follows, an

induction agent, most commonly thymoglobulin or methylprednisolone, is employed

during the perioperative period to rapidly decrease T-cell activity.48 This is coupled by a

maintenance regimen utilized post-operatively in the long-term. The most frequently

13
utilized maintenance regimen consists of triple therapy with a calcineurin inhibitor (most

commonly tacrolimus), mycophenolate mofetil, and corticosteroids. This triad has proven

effective at maintaining graft survival, however patients are at risk of harmful side effects

incurred from immunosuppression including predisposition to metabolic disturbances,

opportunistic infections, renal complications, and malignancies among others over the

long term.3,49,50 A comprehensive review by Huelsboemer et al. examining

immunosuppression regimens and outcomes across 45 face transplantation patients

globally identified that 42.2% of patients incurred opportunistic infection, most

commonly by CMV, 22.2% of patients incurred renal complications (e.g. acute kidney

failure), and 22.2% incurred metabolic derangements (e.g. hypercholesterolemia).48 It is

also important to note that even with an appropriate maintenance immunosuppression

regimen in place the majority of patients incur at least one episode of acute rejection

(73.3%) most often in their first-year post-transplantation, highlighting the need for

ongoing clinical surveillance and continual adjustments in immunosuppression regimen

dosing. Thus, while immunosuppression is the cornerstone of graft maintenance, it

inherently introduces a precarious balance between graft tolerance and systemic health

risks, reflecting the ongoing ethical health challenges of the field.51,52

Another prominent challenge in face transplantation is the availability of suitable

donors and the process of matching them to recipients. Selecting an appropriate donor

involves not only immunologic compatibility—such as ensuring HLA matching and

avoiding pre-formed anti-donor antibodies—but also matching skin tone, tissue

thickness, and facial dimensions to achieve acceptable functional and aesthetic

outcomes.20,53,54 This consideration is especially amplified in non-white face transplant

14
recipients that require careful matching to a donor of the same perceived skin

color/tone.55 Additionally, donor identification requires coordination with organ

procurement organizations, as well as sensitive communication with donor families, who

must provide informed consent for a visible donation unlike with solid organ

transplantation.56,57

In addition to immunological and donor-related hurdles, the financial implications

of face transplantation are substantial. While quantitative cost analyses are variable in the

published literature, multiple studies acknowledge that the initial procedure,

postoperative care, immunosuppression, and ongoing rehabilitation (including physical

therapy, speech therapy, and psychosocial support) incur extensive resources often

extending over $350,000 through the first post-transplant year alone.58,59 As a result, the

majority of face transplants performed thus far have been funded by private hospital

entities or through research grants. However, these costs are not only financial in nature.

Long-term follow-up requires frequent clinic visits, immunological surveillance, and

graft monitoring, placing a considerable burden on both healthcare systems and patients

who must remain highly engaged in their own care indefinitely.1,22,60 Advancement of

face transplant referral networks, program infrastructure, and procedure standardization

in the future may help to ameliorate the extensive monetary and personal costs of this

procedure and increase its feasibility/availability to a greater patient population.2,61,62

Impacts of Facial Ptosis

Despite the procedure’s capacity for dramatically improving facial form and

function, the majority of patients that undergo face transplantation require secondary

15
revision procedures to further optimize functional and aesthetic results. These secondary

revisions have been utilized to address a number of concerns including craniofacial

skeleton and dental malocclusion, necrotic tissue debridement, facial nerve branch repair,

and scar contracture release among many other indications.63,64 However, one of the most

commonly reported indications for secondary revision has been excessive soft tissue

laxity and facial ptosis.64 While facial ptosis is a well-documented phenomenon that

occurs over decades of aging,65-68 postoperative facial ptosis in face transplantation is

impacted by a combination of additional factors that affect both the soft tissues and the

underlying musculoskeletal support. For instance, incomplete or delayed neuromuscular

reinnervation post-transplantation can result in asymmetric muscle tone and diminished

facial support, further potentiating the downward pull of gravity on the facial tissue over

time.69 Additionally, during face transplantation the native retaining ligamentous

structures of the face are often disrupted when the donor allograft is harvested.20,70

Understanding where and to what degree facial ptosis is occurring in the facial allograft is

essential for not only addressing aesthetic outcomes but more importantly functional

ones. Significant facial ptosis in the eyelid and eyebrow region can impede patient visual

fields, while ptosis in the lower portions of the face surrounding the oral commissures

may impact patients’ abilities to eat, swallow, and appropriately retain food and saliva

inside the mouth.

Especially as a subset of the global face transplant patient population ages into

their second decade of life post-transplantation, the need to characterize the extent of this

facial ptosis and its evolution over time becomes more critical. In this study we seek to

provide a quantitative assessment of facial ptosis following face transplantation.

16
Understanding the degree and timing with which tissue ptosis occurs in different

components of the facial allograft can help guide surgical decision-making for

necessitated secondary revision procedures. In addition, this data can help to identify

facial regions predisposed to increased risk for ptosis development, which may allow for

respective adaptions in primary surgical techniques.

Statement of Purpose

The purpose of this study is to characterize the degree of facial ptosis (facial soft

tissue laxity) that occurs over time with the facial allograft following successful face

transplantation. This study intends to address this knowledge gap with the following

specific aims:

Aim 1: Utilizing cephalometric measurements and facial landmarks, quantitatively

characterize the amount of facial ptosis present in the facial allograft postoperatively

1.1- Determine how the measured facial ptosis changes over time as the facial

allograft ages over a multi-year follow up period

1.2- Identify if specific anatomical regions of the face (upper, middle, lower)

experience more or less degrees of facial ptosis relative to others

1.3- Evaluate the extent of facial ptosis progression in comparison to a cohort

of non-face transplanted aged human subjects

With these aims and considerations in mind, we hypothesize that the degree of facial

ptosis in the facial allograft will increase over time and that the ptosis will be expressed

17
globally across all regions (upper, middle, lower) of the face as opposed to isolated to just

one.

Methods

I. Student Contribution

Sam Boroumand fully led the conception, planning, data gathering and

organization, statistical analysis, and execution of the research outlined in this thesis.

Longitudinal patient follow-up images utilized for analysis were acquired from a

database established by multiple previous researchers over a decade at the Brigham and

Women’s Hospital under the direction of Dr. Bohdan Pomahac.

II. Ethics Statement

This research was conducted in accordance with the highest ethical standards. All

methods and procedures were reviewed and approved by the appropriate Institutional

Review Board (IRB). Throughout the study, care was taken to protect the confidentiality

and privacy of all collected data from patients. This manuscript upholds all ethical

standards including ensuring originality, accuracy, transparency, and proper attribution.

No conflicts of interest are reported.

III. Human Subjects Research

This research was approved by the local Institutional Review Boards at Yale New

Haven Hospital (IRB #2000030847) and fully complies with all relevant guidelines,

regulations, and ethical principles governing human subjects research. All patients in this

18
study provided written informed consent for utilization and publication of identifying

clinical photographs.

IV. Laboratory Animals

No animal subjects were utilized for this research.

V. Methods Description

Patient Population

The patient cohort for this study consists of nine face transplant patients (seven

male, two female) that have received their procedure and care under Dr. Bohdan

Pomahac at the Brigham and Women’s Hospital and subsequently Yale New Haven

Health Hospital. Institutional review board approval was obtained prior to study initiation

(Yale IRB# 2000030847). All patients have previously provided written informed

consent for the inclusion and analysis of their photographs and personal medical history

for this study. For each patient, detailed face transplant history was extracted from their

electronic health record including mechanism of original facial injury, extent of facial

defect, components included in facial allograft, date of operation, patient age at time of

operation, significant complications, and details of any post-transplantation revision

procedures.

Study Design

For each face transplant patient, standardized frontal facial photos were taken

post-transplantation at regular follow-up appointments. Photos at 1 year (T0), 3 years

19
(T1), and most recent available follow-up (T2) post-transplantation were collected for

analysis. Additionally, to compare the facial ptosis resulting from face transplantation to

that of natural aging a separate cohort of 10 non-face transplant human subjects were

identified from a publicly available portrait repository to be utilized as a comparative

“control” group.71 Each individual in this group had two standardized frontal facial

photos taken over 70 years apart to maximally capture impacts of aging.

Photometric Analysis of Cephalometric Landmark Measurements

Multiple measurements across the upper, middle, and lower aspects of the face

were taken to evaluate the degree of facial ptosis present. These measurements have been

adapted from previous studies that have demonstrated their utility in evaluating facial

ptosis from aging. All measurements were captured as either intra-facial ratios between

linear measurements of facial landmarks or as angled measurements between facial

landmarks. Thus, all reported measurements are unitless and standardized to each

individual’s unique facial proportions. This allows for balanced comparisons in facial

ptosis evaluations between patients and removes the confounder of image scale or the

distance the patient was to the camera itself. The facial ptosis metrics that were utilized

are listed below and represented in Figure 2.

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Figure 2. Cephalometric landmarks to measure facial ptosis. Highlighted facial angles and
ratios utilized to quantitatively assess facial ptosis: (a) Eyebrow peak angle- angle created by
highest peak of eyebrow arch to medial side of eyebrow to perpendicular horizontal plane. (b)
Eyebrow tail angle- angle created by lowest lateral portion of eyebrow arch to medial side of
eyebrow to perpendicular horizontal plane. (c) Vertical eyelid-iris ratio – ratio of the maximal
height between upper and lower eyelid to the diameter of the iris. (d) Lateral canthus-oral-nasal
angle- angle created by the facial attachment point of the nasal ala to the oral commissure to
the lateral canthus of the same laterality eye. (e) Bigonial-bizygomatic ratio- ratio of the facial
width at the level of the oral commissures to the facial width at the level of the zygoma arches.
(f) Ergotrid length-upper lip ratio- ratio of the ergotrid length to the combined ergotrid and
upper lip length. Except for centralized measures (bigonial-bizygomatic ratio and ergotrid
length-upper lip ratio) all metrics were assessed bilaterally. Patient model adapted with
permission from Tasigiorgos S, Kollar B, Turk M, et al. Five-Year Follow-up after Face
Transplantation. N Engl J Med. 2019;380(26):2579-2581. Copyright Massachusetts Medical
Society.

21
• Upper Face Region:

o Eyebrow Peak Angle- this is a measure of the angle created between the

following three points: highest peak of the eyebrow, medial edge of

eyebrow, and a 180° line from the medial edge of eyebrow parallel to the

ground as depicted in Figure 2a.72 This measure will decrease as the

extent of eyebrow ptosis increases.

o Eyebrow Tail Angle- this is a measure of the angle created between the

following three points: lateral tail of eyebrow, medial edge of eyebrow,

and a 180° line from the medial edge of eyebrow parallel to the ground as

depicted in Figure 2b.72 This measure will increase as the extent of

eyebrow ptosis increases.

o Vertical Eyelid-Iris Ratio- this is measure of how much ptosis of the

eyelid invades over the ocular field and is determined as a ratio of the total

vertical height between the superior and inferior margins of the eyelid

relative to the diameter of the iris as depicted in Figure 2c. This measure

will decrease as the extent of eyelid ptosis increases and is a unitless

adaptation of the marginal reflex distance used to evaluate eyelid ptosis.73

• Middle Face Region:

o Lateral Canthus-Oral-Nasal Angle- this is a measure of the angle created

between the following three points: lateral canthus of the eye, oral

commissure of the mouth, and lateral edge of nasal ala at its attachment

22
 site as depicted in Figure 2d.72 This measure will decrease with increased

facial ptosis.

o Ergotrid Length-Upper Lip Ratio- this is a ratio of the center vertical

length of the ergotrid from the attachment of the nasal septum relative to

the complete vertical length from the same attachment point of the nasal

septum to the inferior border of the upper lip as depicted in Figure 2f.74

This measure will increase with increased facial ptosis.

• Lower Face Region:

o Bigonial-Bizygomatic Ratio- this is a ratio between two measurements,

the first being the bigonial face width at the level of the oral commissure

and the second being the bizygomatic face width at the peak level of the

zygomatic processes as depicted in Figure 2e.75 This measure will

increase with increased facial ptosis (i.e. increased “jowls”).

All facial ptosis measurements outlined above were taken bilaterally on each side

of the face with the exception of the ergotrid length-upper lip ratio and the bigonial-

bizygomatic ratio which are centralized measures. Note that all upper face region

measurements are only applicable to those patients who underwent full face transplants as

partial face transplants do not include the upper brow/eyelid region. Additionally, the

vertical eyelid-iris ratio is only applicable to full face transplant patients who have fully

intact ocular/visual fields (i.e. full face transplant patients with previous traumas resulting

in blindness or enucleation of eye were not included). Analysis of the photos were

23
completed with ImageJ, an open-source software for processing and analyzing scientific

images. This methodology has been documented in previous studies that have utilized the

image analysis software to measure and characterize various anthropometric dimensions

of the face.73,76-78 To minimize user bias with ImageJ, patient photographs were presented

in a randomized order with time points from when the images were taken de-identified

until after all measurements were taken.

VI. Statistical Methods

To evaluate changes in various facial ptosis metrics of the nine face transplant

patients across the three time points (T0, T1, T2), Friedman’s test was employed. Among

those facial ptosis metrics that showed statistically significant changes over time, post-

hoc Dunn’s multiple comparison tests were performed to determine which specific time

intervals had significant changes. This same statistical approach was additionally

employed in select facial ptosis metrics with sufficient n to compare the same three time

points for each sub-group of face transplant patients: those that received bony

components in their facial allograft and those that received strictly myocutaneous (soft

tissue only) allografts. The degree of facial ptosis change was then compared between the

two sub-groups descriptively (n£5 for each subgroup). To evaluate changes across the

two time points (T1, T2) for the non-face transplant subjects, Wilcoxon signed rank test

was employed. Finally, to compare the degree of facial ptosis change seen from T1 to T2

between the face transplant cohort and the non-face transplant human subjects (i.e.

determine which group had significantly greater changes), Mann-Whitney test was

employed. All continuous variables were descriptively presented as the median alongside

24
the interquartile range (IQR). All p-values were two-tailed and those less than 0.05 were

deemed significant. All analyses were conducted in GraphPad Prism version 10.4.1.

Results

Across the 9 face transplantations included in this study, 5 were full face

transplants and 4 were partial face transplants. Demographic and characteristic

information for each patient is outlined in Table 1. The median time to the most recent

follow-up (T2) among patients was 9 years (IQR: 5.5). Additionally, Table 2 provides a

comprehensive accounting of all secondary revision procedures the face transplant cohort

underwent in the post-operative months following their transplantation surgery.

25
 Table 1. Detailed characteristics of face transplant patients included in study.
Demographic and clinical details provided of each of the nine face transplant patients assessed
for facial ptosis in this study.

Patient Gender Transplant Age Mechanism Allograft Mandible/Ma Induction Maintenance Status
Date of Injury Extent xilla in Immuno- Immunosuppression
Allograft? suppression
1 Male 04/2009 59 Electrical Partial Yes; Maxilla Thymoglobulin Tacrolimus Deceased
Burn Mycophenolate Mofetil (2019)
Prednisone
2 Male 03/2011 25 Electrical Full No- Thymoglobulin Tacrolimus Deceased
Burn myocutaneous Mycophenolate Mofetil (2024)
only Prednisone
3 Male 04/2011 30 Electrical Full No- Thymoglobulin Tacrolimus Alive
Burn myocutaneous Mycophenolate Mofetil
only Prednisone
4 Female 05/2011 57 Animal Full Yes; Maxilla Thymoglobulin Tacrolimus Alive
Attack Mycophenolate Mofetil
Prednisone
5 Female 02/2013 45 Chemical Full No- Thymoglobulin Tacrolimus Alive; Re-
Burn myocutaneous Mycophenolate Mofetil transplant
only Prednisone (2020)
due to
chronic
rejection
6 Male 03/2014 39 Ballistic Partial Yes; Mandible Thymoglobulin Tacrolimus Alive
Trauma & Maxilla Mycophenolate Mofetil
Prednisone
Belatacept
7 Male 10/2014 33 Ballistic Partial Yes; Mandible Thymoglobulin Tacrolimus Alive
Trauma & Maxilla Mycophenolate Mofetil
8 Male 06/2018 61 Ballistic Partial Yes; Mandible Thymoglobulin Tacrolimus Deceased
Trauma & Maxilla Mycophenolate Mofetil (2024)
Prednisone
9 Male 07/2019 68 Motor Full No- Thymoglobulin Tacrolimus Alive
Vehicle myocutaneous Mycophenolate Mofetil
Accident only Prednisone
Belatacept

26
 Table 2. Revision procedures of face transplant patients. A detailed timeline and
accounting of all revision procedures underwent by the nine face transplant patients
highlighted in this study. Rows highlighted in bold specifically indicate revision procedures
focused on addressing ptosis or soft tissue laxity of the facial allograft. SMAS, superficial
musculoaponeurotic system; TMJ, temporomandibular joint

Patient Post-operative Indication for Revision Procedure Revision Procedure Performed

Month
Patient 1 1, 6, 7, 24 Redundant soft tissue Bilateral cheek scar revision
1 Tracheocutaneous Fistula Fistula Closure
6 Underprojection of chin Chin implant placement
7 Fistula of right middle canthus Partial opening of tarsorrhaphy incision and
local flap
19 Exposure keratitis Partial tarsorrhaphy of right eye
19 Skin revision and under projection Medpor chin implant placement,
of chin resuspension of bilateral cheeks,
advancement and tightening of skin, lower
lip bilateral musculomucosal flaps
21 Exposure keratitis Complete right eye tarsorrhaphy
22 Ectropion of right lower lid Ectropion correction
24 Laxity of lower cheeks Allograft skin resuspension
35 Recurrent parotitis Duct dilation of left parotid
37 Needed accommodation of denture Deepening of inferior lip sulcus
37 Right infraorbital epidermal inclusion Cyst excision
cyst
98 Cyst of posterior scalp Cyst excision
Patient 2 4 Rehabilitation of dentition Placement of maxillary and mandibular
implants
4 Right eyelid ptosis Ptosis revision
4 Irregular neck contour Revision of left neck skin and subcutaneous
neck tissue
4 Intraoral contracture Bilateral coronoidectomy
4 Excess laxity of skin Local tissue rearrangement, eyebrow lift,
lateral and medial canthopexy
9 Excess skin laxity Excess skin and soft tissue excision with
plication of SMAS
9 Intraoral contracture Z-plasty release
9 Right sided skin laxity Excision of redundant skin, face lift with
SMAS plication, lateral canthopexy of right
eye
13 Rehabilitation of dentition Dental implants

27
 13 Excess skin laxity Reduction and tightening of skin
18 Rehabilitation of dentition Osseointegration
18 Excess laxity of skin SMAS plication with bilateral coronal
eyebrow lift, skin reduction in right eyelids,
resection and tightening of neck skin on left
side
31 Internal submucosal contracture of Contracture release
TMJ
42 Contour abnormalities and Medial canthus V-Y advancement and
progressive facial volume loss medial canthopexy, face and neck lift, fat
grafting
42 Nasal stenosis Nasal obstruction and scar correction
Patient 3 10 Excess laxity of skin Redundant tissue resection, bilateral facelift,
local tissue rearrangement
26 Asymmetry of nose and bone Recontouring of nasal bone
overgrowth
26 Titanium plate in place Titanium plate removal
26 Irregular neck contour Revision of neck skin and recontouring
42 Exposure of eye conjunctiva due to Medial canthus bilateral V-Y advancement
lower eyelid ptosis
Patient 4 8, 11, 15 Palatal fistulas Closure of fistulas
8, 11 Fistula of orbital floor Closure of fistula
11 Delayed recovery of facial motor Nerve transfer of masseter nerve to facial
function nerve
39 Hypertrophic tracheotomy scar Scar revision
39 Left maxillary sinus recurrent Endoscopic opening of sinus
infections
41 Chronic sinusitis of right maxillary Endoscopic maxillary antrostomy
sinus
58 Chronic right frontal mucocele Endoscopic drainage of mucocele
Patient 5 1 Difficulty breathing Division of bilateral nasal synechia and septal
splinting
4 Ectropion of lower eyelid Bilateral tarsal strip canthoplasty
4 Contracture of right neck scar Z-plasty of neck
4 Contracture of left upper lip Z-plasty of left upper lip
15 Nasal stenosis and intranasal Removal of scar tissue and release of intranasal
contracture contracture
15 Bilateral lower eyelid ectropion Ectropion repair
15 Right upper eyelid ptosis Reattachment of upper eyelid levator,
redundant skin excision
15 Lower lip laxity Resuspension of lower lip
15 Right neck contracture Contracture release

28
 15 Left-sided intraoral contracture Z-plasty of contracture
89 Chronic rejection of facial allograft Replacement of facial allograft from new donor
Patient 6 21 Excessive liposity of submandibular Debulking of neck region of facial allograft
areas
21 Redundant nasal tissue along the Resection of redundant tissue
glabellar region
32 Redundant allograft skin Suction lipectomy of the face and epicanthus
reduction
Patient 7 6 Dehiscence and left-sided oral palatal Washout of neck and reclosure of buccal
fistula to neck palatal dehiscence
6 Limited range of mandibular motion Removal of hardware with left total
condylectomy
6 Facial laxity Resuspension of right facial allograft with
fat grafting
Patient 8 0 Nerve disruption of left facial buccal Facial nerve reconstruction
branch
0 Venous insufficiency Re-anastomosis of right retromandibular vein
2 Excess laxity of skin Debulking of facial allograft, right medial
canthus repair
8 Right blocked tear duct and fistula Fistula closure, right dacryocystorhinostomy
formation and right maxillary sinusotomy with nasontral
window
21 Correction of facial contour Rotational zygoma corrective ostomy
21 Right medial canthal laxity Medial canthoplasty
Patient 9 21 Excess skin laxity and ptosis Excision of left upper eyelid skin fold, Z-
plasty of right upper eyelid, open brow lift,
facelift

Face Transplant Facial Ptosis Measurements

Figure 3 highlights various facial ptosis metrics of the upper face measured over

time among the face transplant cohort. Significant changes were noted between median

values at T1 and T2 when examining the left eyebrow peak angle (T1: 28.54° vs T2:

20.98°, p=0.0239), left eyebrow tail angle (T1: 7.01° vs T2: 15.32°, p=0.0085), and right

eyebrow tail angle (T1: 6.30° vs T2: 15.53°, p=0.0008). There was no significant

difference noted between median values at T1 and T2 when examining the right eyebrow

peak angle (T1: 27.79° vs T2: 20.59°, p=0.1821), left vertical eyelid-iris ratio (T1: 0.65

vs T2: 0.62, p=0.1944), and right vertical eyelid-iris ratio (T1: 0.76 vs T2: 0.59,

29
p=0.8333). Important to note that the left and right vertical eyelid-iris ratios had very

limited n (n=3 and n=2, respectively). Figure 4 highlights various facial ptosis metrics of

the middle and lower face measured over time among the face transplant cohort.

Significant changes were noted between median values at T1 and T2 when examining the

left lateral canthus-oral-nasal angle (T1: 42.80° vs T2: 37.72°, p<0.0001), bigonial-

bizygomatic ratio (T1: 0.87 vs T2: 0.91, p=0.0007), and ergotrid length-upper lip ratio

(T1: 0.77 vs T2: 0.83, p=0.0007). There was no significant difference noted between

median values at T1 and T2 when examining the right lateral canthus-oral-nasal angle

(T1: 42.68° vs T2: 37.11°, p=0.0689). Across all facial ptosis metrics evaluated in the

upper, middle, and lower face there was no significant difference between T0 and T1

timepoints (p>0.05). Supplementary Table 1 provides a detailed accounting of the net

differences between each time point across all facial ptosis metrics. Sub-analysis of the

cohort comparing a subset of applicable facial ptosis metrics between patients with bony

components included in their allograft versus myocutaneous only allografts is highlighted

in Table 3. Of note, across the metrics that showed significant changes between T1 and

T2 in both subgroups (left lateral canthus-oral-nasal angle and ergotrid length- upper lip

ratio), the patient cohort with primarily myocutaneous allografts had a greater overall

ptotic change than those that included bony components. Given the very limited sample

size (n£5), formal statistical analysis was not able to be performed to ascertain the

significance median ptotic change between the two different allograft groups, however

descriptively the data highlights this trend when examining the left lateral canthus-oral-

nasal angle (bony allograft T1àT2: -4.23° vs myocutaneous allograft T1àT2: -8.67°)

30
 and the ergotrid length- upper lip ratio (bony allograft T1àT2: +0.07 vs myocutaneous

allograft T1àT2: +0.09).

a. Eyebrow Peak Angle (L)

b.
Eyebrow Peak Angle (R)
40 ✱ 40

30 30

Degrees
Degrees
20 20

10 10

0 0
T0 T1 T2 T0 T1 T2
Timepoint Timepoint

c. Eyebrow Tail Angle (L)

d. Eyebrow Tail Angle (R)
40
40

30
30 ✱
✱✱
Degrees
Degrees

20
20

10
10

0
0
T0 T1 T2
T0 T1 T2
Timepoint Timepoint

e. f.
Vertical Eyelid-Iris Ratio (L) Vertical Eyelid-Iris Ratio (R)
1.0 1.0

0.9 0.9

0.8 0.8
Ratio

Ratio

0.7 0.7

0.6 0.6

0.5 0.5
T0 T1 T2 T0 T1 T2
Timepoint Timepoint

Figure 3. Upper facial ptosis measurements of face transplant patients across multiple
timepoints. Individual metrics were utilized to assess facial ptosis in upper regions of the face across
the face transplant patient population at three time points: T0- 1 year post transplantation, T1- 3 years
post transplantation, T2- most recent follow-up available post transplantation (median: 9 years, IQR:
5.5). Note these metrics only applied to those patients who underwent full face transplants which
naturally includes upper regions of the face. n=5 for a-d., n=3 for e., n=2 for f. IQR, Interquartile
Range; (L), left; (R), right. *p<0.05, **p<0.005.

31
a. b.
Lateral Canthus-Oral-Nasal Angle (L) Lateral Canthus-Oral-Nasal Angle (R)
60 ✱✱✱ 60

45 45
Degrees

Degrees
30 30

15 15

0 0
T0 T1 T2 T0 T1 T2
Timepoint Timepoint

c. d.
Bigonial-Bizygomatic Ratio Ergotrid Length- Upper Lip Ratio
✱✱
1.0 1.0 ✱✱

0.9 0.9

0.8 0.8
Ratio

Ratio

0.7 0.7

0.6 0.6

0.5 0.5
T0 T1 T2 T0 T1 T2
Timepoint Timepoint

Figure 4. Middle and lower facial ptosis measurements of face transplant

patients across multiple timepoints. Individual metrics were utilized to assess facial
ptosis in middle and lower regions of the face across the face transplant patient
population at three time points: T0- 1 year post transplantation, T1- 3 years post
transplantation, T2- most recent follow-up available post transplantation (median: 9
years, IQR: 5.5). n=9 for a-d. (L), left; (R), right. **p<0.005, ***p<0.0005.

32
 Supplementary Table 1. Facial ptosis measurements of face transplant patients across multiple
timepoints. Ten individual metrics were utilized to assess facial ptosis across the face transplant
patient population at three time points: T0- 1 year post transplantation, T1- 3 years post
transplantation, T2- most recent follow-up available post transplantation (median: 9 years, IQR: 5.5).
Net differences between each time point interval were calculated. IQR, Interquartile Range; (L), left;
(R), right. *Indicates p<0.05 with post-hoc Dunn’s multiple comparison tests. Values highlighted in
bold indicate p<0.05.

Metric n Median T0 Median T1 Median T2 p-value Net Difference Net Difference

Value (IQR) Value (IQR) Value (IQR) (T0 à T1) (T1 à T2)
Eyebrow Peak Angle (L) 5 27.01 (8.12) 28.54 (9.27) 20.98 (7.25) 0.0239 +1.53 -7.56*
Eyebrow Peak Angle (R) 5 21.20 (8.91) 27.79 (9.51) 20.59 (8.37) 0.1821 +6.59 -7.20
Eyebrow Tail Angle (L) 5 7.53 (12.28) 7.01(6.36) 15.32 (12.15) 0.0085 -0.52 +8.31*
Eyebrow Tail Angle (R) 5 8.17 (10.05) 6.30 (8.03) 15.53 (9.92) 0.0008 -1.87 +9.23*
Vertical Eyelid-Iris 3 0.86 (0.35) 0.65 (0.32) 0.62 (0.20) 0.1944 -0.21 -0.03
Ratio (L)
Vertical Eyelid-Iris 2 0.70 (0.37) 0.76 (0.22) 0.59 (0.03) -- +0.06 -0.17
Ratio (R)
Lateral Canthus-Oral- 9 41.43 (6.10) 42.80 (3.21) 37.72 (7.00) <0.0001 +1.37 -5.08*
Nasal Angle (L)
Lateral Canthus-Oral- 9 42.68 (10.33) 42.96 (9.57) 37.11 (5.35) 0.0689 +0.28 -5.85
Nasal Angle (R)
Bigonial-Bizygomatic 9 0.89 (0.03) 0.87 (0.07) 0.91(0.06) 0.0007 -0.02 +0.03*
Ratio
Ergotrid Length- Upper 9 0.82 (0.15) 0.77 (0.12) 0.83 (0.11) 0.0007 -0.06 +0.06*
Lip Ratio

33
 Table 3. Comparison of select facial ptosis measurements between face transplant patients
with bony vs only myocutaneous allografts. Four select facial ptosis metrics with sufficient n
were assessed between face transplant patients that received bony vs only myocutaneous
allograft at three time points: T0- 1 year post transplantation, T1- 3 years post transplantation,
T2- most recent follow-up available post transplantation (median: 9 years, IQR: 5.5). IQR,
Interquartile Range; (L), left; (R), right.

Metric n Median T0 Median T1 Median T2 p-value Net Difference Net Difference

Value (IQR) Value (IQR) Value (IQR) (T0 à T1) (T1 à T2)
PATIENTS WITH MAXILLA/MANDIBLE INCLUDED IN ALLOGRAFT
Lateral Canthus-Oral- 5 40.38 (7.34) 41.95 (3.96) 37.72 (7.30) 0.0008 +1.57 -4.23
Nasal Angle (L)
Lateral Canthus-Oral- 5 42.68 (9.61) 42.96 (7.66) 37.18 (13.72) 0.1821 +0.28 -5.78
Nasal Angle (R)
Bigonial- 5 0.91 (0.05) 0.90 (0.08) 0.91 (0.06) 0.0085 -0.01 +0.01
Bizygomatic Ratio
Ergotrid Length- 5 0.76 (0.17) 0.74 (0.17) 0.81 (0.10) 0.0394 -0.01 +0.07
Upper Lip Ratio
PATIENTS WITHOUT BONY ALLOGRAFT (MYOCUTANEOUS ONLY)
Lateral Canthus-Oral- 4 43.02 (6.17) 43.43 (3.78) 34.76 (9.28) 0.0417 +0.41 -8.67
Nasal Angle (L)
Lateral Canthus-Oral- 4 41.48 (14.52) 42.90 (16.41) 36.06 (4.48) 0.4306 +1.42 -6.84
Nasal Angle (R)
Bigonial- 4 0.89 (0.09) 0.87 (0.07) 0.90 (0.08) 0.1250 -0.02 +0.03
Bizygomatic Ratio
Ergotrid Length- 4 0.85 (0.12) 0.81 (0.12) 0.90 (0.08) 0.0417 -0.05 +0.09
Upper Lip Ratio

34
Non-Face Transplant Subjects Facial Ptosis Measurement

Across the 10 non-face transplant human subjects included in this study 5 were

males and 5 were females. Information on the ages of each subject at each time point

evaluated is outlined in Table 4. The median age at T1 of this cohort was 23.0 (IQR: 5.0),

while the median age at T2 was 101.5 (IQR:1.0) reflecting a median age difference

between the two timepoints of 78.0 (IQR: 5.0).

Table 4. Demographic characteristics of non-face transplant aged human subjects.

Gender and age demographics of ten human subjects who did not receive face
transplants evaluated for facial ptosis at two timepoints, T1 and T2. IQR, Interquartile
Range.

Subject Gender Younger Age at T1 Older Age at T2 Age Difference

1 Male 25 102 77
2 Male 17 101 84
3 Male 17 102 85
4 Male 30 105 75
5 Male 20 102 82
6 Female 23 101 78
7 Female 23 101 78
8 Female 30 100 70
9 Female 23 101 78
10 Female 22 102 80
Median (IQR) -- 23.0 (5.0) 101.5 (1.0) 78.0 (5.0)

35
 Figure 5 highlights facial ptosis metrics of the upper face measured at two time

points among this non-face transplanted cohort. Significant changes were noted between

median values at T1 and T2 when examining the left eyebrow peak angle (T1: 15.60° vs

T2: 13.70°, p=0.0020), right eyebrow tail angle (T1: 16.14° vs T2: 14.91°, p=0.0020), left

eyebrow tail angle (T1: 9.06° vs T2: 16.97°, p=0.0020), right eyebrow tail angle (T1:

8.80° vs T2: 14.20°, p=0.0020), left vertical eyelid-iris ratio (T1: 0.91 vs T2: 0.74,

p=0.0020), and right vertical eyelid-iris ratio (T1: 0.97 vs T2: 0.75, p=0.0020). Figure 6

highlights facial ptosis metrics of the middle and lower face measured at two time points

among this non-face transplanted cohort. Significant changes were noted between median

values at T1 and T2 when examining the left lateral canthus-oral-nasal angle (T1: 51.98°

vs T2: 45.68°, p=0.0020), right lateral canthus-oral-nasal angle (T1: 45.72° vs T2: 39.57°,

p=0.0371), bigonial-bizygomatic ratio (T1: 0.85 vs T2: 0.90, p=0.0020), and ergotrid

length-upper lip ratio (T1: 0.74 vs T2: 0.87, p=0.0020). Supplementary Table 2 provides

a detailed accounting of the net differences between the two time points of this non-face

transplanted cohort across all facial ptosis metrics.

Face Transplant vs Non-Face Transplant Facial Ptosis Comparison

Figure 7 provides a comparison of the median change in various upper facial

ptosis metrics from T1 to T2 of the face transplant cohort compared to the non-face

transplant human subjects. There was no significant difference across any of the upper

facial ptosis metrics when comparing the median degree of ptotic change from T1 to T2

between the face transplant and non-face transplant cohorts which included the left

eyebrow peak angle (-5.98° vs -3.87°, p=0.3097), right eyebrow peak angle (-3.66° vs -

36
1.61°, p=0.2065), left eyebrow tail angle (+4.74° vs +7.01°, p=0.5941), right eyebrow tail

angle (+3.73° vs +4.84°, p=0.7679), left vertical eyelid-iris ratio (-0.03 vs -0.15,

p=0.0769), and right vertical eyelid-iris ratio (-0.17 vs -0.22, p=0.7576). Figure 8

provides a comparison of the median change in various middle and lower facial ptosis

metrics from T1 to T2 of the face transplant cohort compared to the non-face transplant

human subjects. The only metric that demonstrated a significantly greater median change

in the non-face transplant subjects relative to the face transplant patients from T1 to T2

was the ergotrid length- upper lip ratio (+0.14 vs +0.07, p=0.0220). All other facial ptosis

metrics of the middle and lower face demonstrated no significant difference when

comparing the median degree of ptotic change from T1 to T2 between the face transplant

and non-face transplant cohorts which included the left lateral canthus-oral-nasal angle (-

4.23° vs -4.74°, p=0.6607), right lateral canthus-oral-nasal angle (-4.43° vs -3.50°,

p=0.8421), and bigonial-bizygomatic ratio (+0.02 vs +0.05, p=0.2775).

37
 a. Eyebrow Peak Angle (L)
b. Eyebrow Peak Angle (R)
30 ✱✱ 30 ✱✱

25 25

20 20

Degrees
Degrees
15 15

10 10

5 5

0 0
T1 T2 T1 T2
Timepoint Timepoint

c. Eyebrow Tail Angle (L)

d. Eyebrow Tail Angle (R)
30
30
✱✱ ✱✱
25
25
20
20
Degrees

Degrees
15
15
10
10
5
5
0
0
T1 T2
T1 T2
Timepoint
Timepoint

e. f.
Vertical Eyelid-Iris Ratio (L) Vertical Eyelid-Iris Ratio (R)
✱✱
✱✱
1.2 1.2

1.0 1.0

0.8 0.8
Ratio

Ratio

0.6 0.6

0.4 0.4

0.2 0.2

0.0 0.0
T1 T2 T1 T2
Timepoint Timepoint

Figure 5. Upper facial ptosis measurements of non-face transplant human

subjects across two timepoints. Individual metrics were utilized to assess facial
ptosis in upper regions of the face from aging across ten non-face transplanted human
subjects at two timepoints: T1- younger age (median: 23, IQR: 5), T2- older age
(median: 101.5, IQR: 1). n=10 for a-f. (L), left; (R), right. **p<0.005. IQR,
interquartile range

38
a. b.
Lateral Canthus-Oral-Nasal Angle (L) Lateral Canthus-Oral-Nasal Angle (R)
80 80 ✱
✱✱

60 60

Degrees

Degrees
40 40

20 20

0 0
T1 T2 T1 T2
Timepoint Timepoint

c. d.
Bigonial-Bizygomatic Ratio Ergotrid Length- Upper Lip Ratio
✱✱ ✱✱
1.0 1.0

0.9 0.9

0.8 0.8
Ratio

Ratio
0.7 0.7

0.6 0.6

0.5 0.5
T1 T2 T1 T2
Timepoint Timepoint

Figure 6. Middle and lower facial ptosis measurements of non-face transplant

human subjects across two timepoints. Individual metrics were utilized to assess
facial ptosis in middle and lower regions of the face from aging across ten non-face
transplanted human subjects at two timepoints: T1- younger age (median: 23, IQR:
5), T2- older age (median: 101.5, IQR: 1). n=10 for a-d. (L), left; (R), right.
**p<0.005. IQR, interquartile range

39
Supplementary Table 2. Facial ptosis measurements of non-face transplant
human subjects across two timepoints. Ten individual metrics were utilized to assess
facial ptosis from aging across ten non-face transplanted human subjects at two
timepoints: T1- younger age (median: 23, IQR: 5), T2- older age (median: 101.5, IQR:
1). IQR, Interquartile Range; (L), left; (R), right. Values highlighted in bold indicate
p<0.05.

Metric Median T1 Median T2 p-value Net Difference

Value (IQR) Value (IQR) (T1 à T2)
Eyebrow Peak Angle (L) 15.60 (8.10) 13.70 (3.64) 0.0020 -1.90
Eyebrow Peak Angle (R) 16.14 (6.75) 14.91 (8.45) 0.0020 -1.23
Eyebrow Tail Angle (L) 9.06 (4.45) 16.97 (6.70) 0.0020 +7.91
Eyebrow Tail Angle (R) 8.80 (1.75) 14.20 (3.42) 0.0020 +5.40
Vertical Eyelid-Iris Ratio (L) 0.91 (0.16) 0.74 (0.22) 0.0020 -0.17
Vertical Eyelid-Iris Ratio (R) 0.97 (0.18) 0.75 (0.22) 0.0020 -0.22
Lateral Canthus-Oral-Nasal 51.98 (10.75) 45.68 (5.31) 0.0020 -6.30
Angle (L)
Lateral Canthus-Oral-Nasal 45.72 (19.21) 39.57 (17.02) 0.0371 -6.15
Angle (R)
Bigonial-Bizygomatic Ratio 0.85 (0.04) 0.90 (0.03) 0.0020 +0.05
Ergotrid Length- Upper Lip 0.74 (0.06) 0.87 (0.11) 0.0020 +0.13
Ratio

40
 a. Eyebrow Peak Angle (L)
b. Eyebrow Peak Angle (R)
5 5

Δ Degrees (T2-T1)

Δ Degrees (T2-T1)
0 0

-5 -5

-10 -10

-15 -15

nt
nt

nt
nt
la
la

la
la
sp
sp

sp
sp
an

an

an

an
Tr

Tr

Tr

Tr
ce

ce

ce
ac
Fa

Fa

a
-F

-F
on

on
N

N
c. Eyebrow Tail Angle (L)
d. Eyebrow Tail Angle (R)
20 20

Δ Degrees (T2-T1)
Δ Degrees (T2-T1)

15 15

10 10

5 5

0 0

nt
nt
nt
nt

la
la
la
la

sp
sp
sp
sp

an

an
an

an

Tr

Tr
Tr

Tr

ce

e
ce

ac
ac

Fa
Fa

-F
-F

on
on

N
N

e. Vertical Eyelid- Iris Ratio (L)

f. Vertical Eyelid- Iris Ratio (R)
0.0 0.0

-0.1 -0.1
Δ Ratio (T2-T1)
Δ Ratio (T2-T1)

-0.2 -0.2

-0.3 -0.3

-0.4 -0.4

-0.5 -0.5
nt
nt
nt
nt

la
la
la
la

sp
sp
sp
sp

an

an
an

an

Tr

Tr
Tr

Tr

ce

e
ce

ac
ac

Fa
Fa

-F
-F

on
on

N
N

Figure 7. Comparison of degree of change in upper facial ptosis metrics between

face transplant patients and non-face transplant human subjects. For each cohort the
median change from T1 to T2 (6 years for face transplant cohort, 78 years for non-face
transplant cohort) was calculated for each upper facial ptosis metric a-f. and then
evaluated between the two cohorts. N=10 for the non-face transplant cohort for all
metrics above. The n for the face transplant cohort for each metric is as follows: a. n=5;
b. n=5; c. n=5; d. n=5; e. n=3; f. n=2. (L), left; (R), right. p>0.05 for all comparisons.

41
a. b.
Lateral Canthus- Oral- Nasal Angle (L) Lateral Canthus- Oral- Nasal Angle (R)
10 10

5 5

Δ Degrees (T2-T1)
Δ Degrees (T2-T1) 0 0

-5 -5

-10 -10

-15 -15

nt
nt
nt
nt

la
la
la
la

sp
sp
sp
sp

an
an
an
an

Tr

Tr
Tr

Tr

ce

ce
ce

e
ac

Fa

a
Fa

-F
-F

on
on

N
N

c. Bigonial- Bizygomatic Ratio

d. Ergotrid Length- Upper Lip Ratio
0.25 0.25 ✱

0.20 0.20

Δ Ratio (T2-T1)
Δ Ratio (T2-T1)

0.15 0.15

0.10 0.10

0.05 0.05

0.00 0.00
nt
nt
nt
nt

la
la
la
la

sp
sp
sp
sp

an
an
an
an

Tr

Tr
Tr

Tr

ce

e
ce

ac
ac

Fa
Fa

-F
-F

on
on

N
N

Figure 8. Comparison of quantity of change in middle and lower facial ptosis

metrics between face transplant patients and non-face transplant human
subjects. For each cohort the median change from T1 to T2 (6 years for face
transplant cohort, 78 years for non-face transplant cohort) was calculated for each
middle and lower facial ptosis metric a-d. and then evaluated between the two cohorts.
N=9 for the face transplant cohort and n=10 for the non-face transplant cohort for all
metrics above. (L), left; (R), right. *p<0.05

42
Discussion

Face transplantation represents a transformative surgical approach, restoring both

functionality and aesthetics in patients with severe facial disfigurements. The twenty

years of advancement and innovation in the field since the first case has spotlighted the

encouraging outcomes and potential of the procedure. Despite its promise, the long-term

behavior of transplanted facial tissues, particularly in relation to ptosis, has not been well-

characterized. Ultimately, this thesis aimed to provide a first-time quantification of the

degree of facial ptosis in transplanted facial allografts over time.

Drivers Impacting Facial Ptosis Change Over Time

Most notably, the results demonstrated that across six of the ten facial ptosis

metrics evaluated (left eyebrow peak angle, left eyebrow tail angle, right eyebrow tail

angle, left lateral canthus-oral-nasal angle, bigonial-bizygomatic ratio, ergotrid length-

upper lip ratio) a significant increase of ptosis was identified between T1 (3 years post-

transplant) and T2 (most recent follow-up post-transplant, median= 9 years) with the

remaining non-statistically significant metrics (right eyebrow peak angle, left vertical

eyelid-iris ratio, right vertical eyelid-iris ratio, right lateral canthus-oral-nasal angle) all

demonstrating trending increases of facial ptosis as well. These results ultimately

highlight a progression of facial ptosis over time and more specifically reveal that this

ptosis is experienced globally across collective components of the upper, middle, and

lower face as opposed to one region. However, when evaluating timepoints T0 (1 year

post-transplantation) to T1 across the face transplant cohort, there was no significant

differences noted across any of the facial ptosis metrics evaluated. This is a particular

43
interesting finding that based on these results in the first three years post-transplantation

there seems to be no significant change in ptosis of the facial allograft. Several etiologies

may be contributing to this phenomenon. The extent of neuromuscular recruitment

alongside dynamic changes in muscle volume of the facial allograft likely impact the

resulting trends we see in facial ptosis. Tasigiorgos et al. conducted a five-year follow-up

of six patients from this study and demonstrated that motor function of the facial allograft

had rapid improvement in the first-year post-transplantation but that this improvement

was significantly decreased after the first year.4 Similarly, using electromyography and

lip motor function scores, De Letter et al. reported improvement in facial motor function

at the 38 month timepoint post-transplantation but did not report on further timepoints.79

Limitations in or incomplete rehabilitation of neuromuscular recruitment over time can

result in muscular atrophy of the facial allograft and subsequently potentiate the degree of

facial soft tissue ptosis that may evolve over time.80 In fact, Kueckelhaus et al. performed

a CT imaging analysis of three patients from this study and noted significant decreases in

non-fat tissue volume over time with definitive histological evidence of muscle atrophy at

the 40 months post-transplantation timepoint.81 Thus reduced improvement in

neuromuscular function or rehabilitation across consecutive years (resulting in facial

muscle atrophy) following face transplantation may help account for the significant facial

ptosis observed over the 9 year median follow-up that is negligible in the immediate 36

months post-transplantation.

A potentially more compelling etiology of this observed facial ptosis trend may be

the pattern and timing of secondary revision procedures. When examining the summary

of secondary revision procedures underwent by the face transplant cohort in Table 2,

44
collectively the nine patients had 27 revision procedures performed in total addressing

soft tissue ptosis or tissue laxity of the facial allograft. In fact, past studies have

highlighted that soft tissue laxity is the most common indication for secondary revision

procedures post-face transplantation.64,82 26 out of those 27 revision procedures were

performed within the first 36 months post-transplantation. This pattern corroborates well

with the non-significant change in facial ptosis observed in the cohort between the 1 year

(T0) and 3 year timepoints (T1). More importantly it provides a quantitative affirmation

that revision procedures addressing facial ptosis (e.g. excess skin excision, brow lift, neck

lift, SMAS plication) are effective. The frontloading of many revision procedures early in

the postoperative timeline of face transplant patients is intentioned strategically. At the

time of face transplantation, often a very liberal approach is taken to include an excess

amount of available donor tissue in the transplanted allograft. The initial allograft inset on

the recipient should provide abundant soft tissue in excess of the base volume required in

order to account for resorption or contracture in parts of the allograft, tolerate

postoperative edema, and ensure tension-free closure of the allograft to the recipient.38

This notion is in particular critical as it relates to transplantation of eyelid subunits and

adjacent periorbital tissues as insufficient tissue in this region can endanger patients to

ectropion or lagophthalmos.38,63,83 Even in the acute timeline, these complications can

result in exposure keratopathy leading to corneal scarring, ulceration, and potential

blindness.38,84 The excess incorporation of periorbital tissues thus ensures complete

closure and coverage of the corneal surface until healing of the allograft is complete with

any potential ocular ptosis able to be addressed through secondary revision procedures

(e.g. tarsorrhaphy, V-Y advancement/repositioning of the medial/lateral canthus).82

45
 The significant increase in facial ptosis from the 3-year to 9-year median follow-

up across several metrics in this patient population ultimately highlights that revision

procedures performed in the first 3 years post-transplantation may not be adequate for

long-term mitigation of tissue laxity and resuspension of the allograft. More specifically,

it demonstrates the continued need for facial ptosis surveillance and utilization of

additional revision procedures even approaching a decade post-transplantation to

optimize allograft functionality and aesthetics. However, it should be noted that while

revision procedures have incredible utility for addressing facial ptosis among many other

post-transplantation complications, they carry with them risks considerable to the face

transplant patient population in particular. The most significant risk being acute rejection

of the facial allograft following surgical revision. The introduction of foreign surgical

instruments, placement of sutures, trauma to the tissue, and subsequent inflammation and

immunological stress incurred by the procedure itself can all serve as corroborating

niduses for triggering acute rejection of the facial allograft, subsequently requiring pulsed

steroid therapy or uptitraton of the immunosuppression regimen to treat.38,63,85 In relation

to this latter point, the requirement of chronic immunosuppression leaves face transplant

patients additionally susceptible to heightened risks of infections and delayed wound

healing following any surgical procedure- effects that have been well-documented in the

literature.38,86-89 The other important consideration for planning revisions or any other

surgical procedure on the facial allograft is the unique anatomy. The donor facial allograft

is inset on the recipient with anastomoses of the external carotid/facial vessels,

coaptations of the trigeminal and facial nerve branches, and potential alignment of

reciprocal osteotomy sites between recipient and donor if bony components are included

46
in the allograft.90 As a result, the resulting facial anatomy of the transplanted donor

allograft on the recipient will vary from native anatomy. Any future surgical procedure on

the allograft must account for these anatomical variations on a case-by-case basis to

avoid detrimentally impacting the neurovascular conduits of the facial allograft.91

Fortunately, the robustness and extensive collateralization of the facial arterial system

additionally helps in this regard to mitigate any significant disruptions to the blood

supply of the allograft.92

Comparison of Facial Ptosis Between Myocutaneous and Bony Allografts

The sub-group analysis comparing face transplant patients who received

maxillary/mandibular bone as part of their facial allograft versus those that did not

(myocutaneous only allograft) highlights some interesting findings. Across the four facial

ptosis metrics that were able to be included in this limited analysis (low n value limited

inclusion of others), all of them demonstrated greater ptotic changes from T1 to T2 in the

myocutaneous allograft group compared to the bony allograft. Given the very limited

sample size (n£5), formal statistical analysis was not able to be performed to ascertain the

significance of this difference, however this preliminary trend offers additional insights

into the biomechanics underlying facial ptosis in face transplantation. As seen with

natural aging, soft-tissue laxity and gravitational droop is known to develop over time.68

In facial tissue specifically, retaining ligaments of the face, as depicted in Figure 9,

provide structural support to the soft tissue by providing anchors to the underlying facial

skeleton and therefor help resist this gravitational pull over time.93,94 However, given the

nature of the operation itself, patients that undergo face transplantation inherently have

47
disruption of these retaining ligaments to varying degrees depending on the operative

approach utilized and type of allograft itself. Greater preservation of these retaining

ligaments can be achieved by incorporating skeletal subunits (i.e. mandible/maxilla) from

the donor into the allograft as well so that they are transplanted as a cohesive unit.38,63

This notion likely explains the trend of decreased facial ptosis from T1 to T2 seen in

patients with allografts that included bony components in comparison to patients with

strictly myocutaneous allografts. Given this understanding, an argument could be made to

have every face transplant candidate receive an allograft with intact skeletal subunits and

retaining ligaments. Although this may improve aesthetics and functionality of the

allograft as it relates to facial ptosis, this likely will require removal of intact facial

structures and skeletal anatomy to accommodate the additional bony subunits.82 This is

an important consideration because if functional, atraumatic skeletal components of the

face are removed to accommodate a bony allograft and the allograft ultimately fails then

patients are left with minimal reconstructive options to replace the native skeletal

components that were removed for the procedure. Additionally, inclusion of skeletal

subunits requires additional bony fixation with plates and screws which can prolong

operative time, recovery, and potentiate the morbidity associated with any complications

from the added hardware.95,96 Balancing these considerations alongside more importantly

the extent of the patient’s facial trauma and reconstructive needs is essential as part of the

pre-operative planning.

48
 Figure 9. Anatomic locations of key facial retaining ligaments. Reproduced with
permission from Alghoul M, Codner MA. Retaining ligaments of the face: review of
anatomy and clinical applications. Aesthet Surg J. 2013;33(6):769-782.
doi:10.1177/1090820X13495405. Copyright Oxford University Press.

Aging Impacts to Facial Ptosis

The processes underlying facial aging have been well-characterized in the

literature, primarily driven by both intrinsic and extrinsic factors that lead to structural

and functional changes in the skin, soft tissues, and underlying skeletal framework.68,93,97-
99
Intrinsically, aging results in a decline in fibroblast activity, collagen production, and

49
elastin integrity, key components of the extracellular matrix that maintain skin elasticity

and tensile strength.68,100 Over time this results in decreased skin elasticity and durability.

Concurrently, there is a gradual atrophy of subcutaneous fat compartments, particularly in

the midface, which results in volume loss and accentuates the prominence of skeletal

landmarks.93,101 This is further exacerbated by age-related bone resorption, particularly in

the maxilla, mandible, and orbital regions.67,102,103 The cumulative impact of all these

processes compounded by the downward gravitational forces on the facial tissue over

time results in the increased tissue laxity, decreased tissue volume, and overall ptotic

appearance of the face that is common with aging. It should be noted that many extrinsic

factors, including ultraviolet radiation exposure, smoking, and air pollution, among many

others can further accelerate the degradation of the skin’s structural components through

oxidative stress and chronic inflammation and potentiate the aging effects.104-106

Appreciating these processes and their impact on facial ptosis helps to contextualize the

findings presented in this study. In the non-face transplanted “control” cohort of 10

human subjects, the results corroborated the expected progression of facial ptosis due to

natural aging. Across all measured metrics, significant increases in ptosis were

appreciated between the two comparison timepoints, providing a quantitative reflection

of the natural aging trajectory as it relates to facial ptosis. It should be especially noted

that the median age difference of 78 years between timepoints in this aged cohort

underscores the pronounced effect of aging on facial ptosis, thus providing a robust

baseline for comparison against the face transplant cohort.

The mechanisms of aging in facial allografts remain less understood, given the

relatively recent implementation of the procedure in just the past two decades and the

50
limited longitudinal data available.82 Most of the living face transplant recipients globally

are within their first decade post-transplantation, leaving significant gaps in knowledge

about the long-term impacts of aging of these transplanted tissues. Additionally, unlike

native tissues, facial allografts are further impacted by factors such as chronic systemic

immunosuppression as well as episodes of acute and/or chronic rejection. The impact

these unique variables may have on the degree of facial ptosis and the facial aging

process as a whole remains unclear. This study’s comparison of facial ptosis progression

between the face transplant cohort and the non-face transplant control cohort yielded

interesting findings. As highlighted in Figure 7 and Figure 8, across 9 out of the 10

facial ptosis metrics evaluated there was no significant difference in the degree of facial

ptosis change between T1 and T2 when comparing the two cohorts. In effect, this

implicates that the overall degree change of facial ptosis experience by the face transplant

cohort from 3 years post-transplant to a median follow-up of 9 years post-transplant (6

year median time interval) is comparable to the degree change of facial ptosis

experienced by the non-face transplanted cohort which had a median aging interval of 78

years between T1 and T2. This finding—notable across all metrics except the ergotrid

length-upper lip ratio—underscores the pronounced and accelerated ptotic changes in

transplanted faces within a comparatively short time span. The potential implication is

considerable that transplanted faces, while transformative in restoring form and function,

are subject to aging dynamics that mimic decades of natural ptotic progression within less

than a decade. The ergotrid length-upper lip ratio was the sole metric where the face

transplant cohort demonstrated a significantly lesser degree of ptotic change compared to

the control group. This is likely in part because the ergotrid length-upper lip ratio

51
significantly increases with downward rolling of the vermillion border that occurs with

natural aging.68,107 This process is primarily driven by loss of fat pads around the

vermillion border that occur with aging. A previous face transplantation imaging study by

Kueckelhaus et al. has highlighted that fat volume remains relatively constant in the

facial allograft over a multi-year follow up period, potentially explaining the decreased

ptotic change captured in this metric relative to the non-face transplant aged cohort.81

Collectively, these results have significant implications for the long-term management of

face transplant patients. This comparative model of accelerated ptosis observed suggests

that routine surveillance and periodic interventions, such as soft tissue resuspension or

volumetric augmentation, may be necessary to maintain aesthetic and functional

outcomes especially as face transplant patients continue to age into their second decade

of life post-face transplantation.

Future Directions

With an aging face transplant recipient population, future studies should focus on

following these patients over additional time points to assess the continued evolution of

facial ptosis. Longitudinal tracking will provide critical insights into whether the

trajectory of ptosis stabilizes, accelerates, or follows patterns akin to natural aging

beyond the current median follow-up of nine years. Further investigations should also

evaluate the efficacy of specific revision procedures in mitigating facial ptosis. By taking

precise measurements of ptosis metrics immediately prior to and following these

procedures, their immediate and long-term effects on facial contour and soft tissue

support can be objectively quantified. Additionally, advancements in 3D imaging

52
capabilities and artificial intelligence (AI) software analysis present another promising

avenue for future research. Scaling these facial ptosis metrics to three-dimensional

models would allow for the capture of greater depth and accuracy in assessing ptotic

changes. This approach would enhance the ability to quantify complex spatial

relationships and subtle asymmetries in facial contours, offering a more comprehensive

understanding of soft tissue dynamics over time. Similar methodologies have been

studied in other applications of cephalometric landmark detection.108-110 AI-driven

analysis could further streamline data processing and provide predictive insights into

ptosis progression and the efficacy of interventions. Incorporating 3D metrics into

clinical practice could significantly improve the precision of assessments and expand

their utility across diverse patient populations, including those undergoing facial

reanimation or treatment for facial paralysis. Expanding the application of these facial

ptosis metrics to other clinical contexts represents another promising avenue. These

metrics could be utilized to assess and quantify facial asymmetry and soft tissue descent

in conditions such as facial paralysis due to stroke or Bell’s palsy. Similarly, they hold

potential in tracking the outcomes of facial reanimation surgeries, providing a

standardized and objective framework for evaluating improvements in symmetry and

function. Such applications would not only broaden the clinical utility of these metrics

but also pave the way for their integration into diverse fields of reconstructive and

rehabilitative medicine.

Challenges & Limitations

53
 This study faced several challenges and limitations, which merit discussion. First,

the relatively small sample size of nine face transplant recipients limits the power and

generalizability of the findings. However, it is worth noting that a little over 50 face

transplants have been conducted worldwide to date. In relation to that figure, this study

includes nearly 20% of the global population of face transplant recipients. Thus, within

the context of the small field itself the contribution of this study to the field is not

insignificant. Another limitation is the lack of age-matched control subjects for each face

transplant recipient to capture facial ptosis over comparable time interval. While such a

photographic dataset would have offered a more precise baseline for comparison, it

unfortunately was not feasible to find or create such a dataset. Nonetheless, the inclusion

of the non-face transplant human subjects group utilized in this study, with individuals

examined over a 70+ year time interval, still provided valuable contextualization for

appreciating the extent of ptosis observed in the face transplant cohort. Additionally, the

methodology has limitations in regards to its subjectivity inherent in measuring

cephalometric landmarks to ascertain facial ptosis across the different metrics utilized.

Even with standardized techniques, subtle variations in landmark identification can

introduce bias. To mitigate this, all measurements in this study were conducted by the

same individual, who performed assessments in a blinded and randomized fashion, with

timepoints de-identified, thereby reducing both bias and inter-subject variability in how

and where precisely the metric landmarks were identified. Finally, the study is limited by

the inability to fully account for the numerous extrinsic factors that influence aging,

including ones that are still not well understood such as the effects of chronic

immunosuppression. These factors may have variably impacted facial ptosis progression

54
across different patients. Unfortunately, this understanding is an accepted limitation of

any model examining facial aging in the literature as it is impossible to control and

account for the many known and unknown extrinsic drivers of facial aging. Despite this

limitation, the study’s findings offer a foundational and comparative understanding of

ptosis dynamics in both transplanted and non-transplanted faces, paving the way for

future research.

Conclusion

This study is the first to provide a direct quantification of the degree of facial

ptosis incurred by face transplant recipients over time. Providing this critical insight into

the progression of facial ptosis in this patient population revealed a significant increase in

ptosis over time that mirrors decades of natural aging within a shorter timeframe. The

comparative ptosis progression across a median 6-year time interval of face transplant

patients to a median 78 year time interval of non-face transplant human subjects

underscores the potentially accelerated aging dynamics of facial allografts as they relate

to facial ptosis. Interestingly, negligible or reduced ptosis in the first three years post-

transplantation offers insights into the potential roles of neuromuscular rehabilitation and

early revision procedures in maintaining soft tissue support. However, the significant

ptosis observed at longer follow-ups underscores the need for continued monitoring and

periodic revisions to sustain aesthetic and functional outcomes. Preliminary findings

suggest that the inclusion of skeletal components in the allograft may mitigate ptosis,

offering avenues for further exploration. Ultimately, this research not only advances the

55
understanding of aging in facial allografts but also provides a foundation for optimizing

surgical techniques and long-term care strategies in face transplantation.

56
Dissemination

Boroumand S, Stogner V, Aquilina S, Huelsboemer L, Vafa AZ, Kauke-Navarro M,

Pomahac M. Quantitative Characterization of Facial Ptosis in Face Transplantation.

Podium Presentation In: American Society of Reconstructive Transplantation; November

2024; New Haven, CT, USA.

Boroumand S, Stogner V, Aquilina S, Huelsboemer L, Vafa AZ, Kauke-Navarro M,

Pomahac M. Quantitative Characterization of Facial Ptosis in Facial Transplantation- A

Single Institution Analysis of Nine Face Transplant Patients. Podium Presentation In:

Plastic Surgery: The Meeting; September 2024; San Diego, CA, USA.

Boroumand S, Vafa AZ, Aquilina S, Stogner V, Huelsboemer L, Kauke-Navarro M,

Pomahac M. Quantitative Characterization of Facial Ptosis in Face Transplantation.

Podium Presentation In: Yale School of Medicine Student Research Day; May 2024; New

Haven, CT, USA.

57
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