Secondary Logo

Journal Logo

Ocular Considerations in Face Transplantation

Report of 2 Cases and Review of the Literature

Greenfield, Jason A., B.A.*; Kantar, Rami S., M; .D.*; Rifkin, William J., B.A.*; Sosin, Michael, M.D.*; Diaz-Siso, J. Rodrigo, M.D.*; Patel, Payal, M.D.; Fleming, James C., M.D.; Iliff, Nicholas T., M.D.§; Lee, Bradford W., M.D., M.Sc.; Rodriguez, Eduardo D., MD, DDS*

Ophthalmic Plastic & Reconstructive Surgery: May/June 2019 - Volume 35 - Issue 3 - p 218–226
doi: 10.1097/IOP.0000000000001296
Major Reviews
Free
SDC

Purpose: Periorbital injuries are common in face transplantation (FT) candidates. It is therefore essential that the ophthalmologist play a central role in the multidisciplinary treatment of these patients. In this study, the authors perform a comprehensive review of all procedures involving periorbital components, provide an update for the ophthalmology community regarding the current state of the field, and present 2 cases.

Methods: A comprehensive review of the literature for all FT procedures including periorbital components was performed. The authors also present 2 patients who received FT including periorbital components for extensive facial disfigurement. One patient sustained high-energy avulsive ballistic injury and underwent a total face, double jaw, and tongue transplant in 2012. The second patient received a total face, eyelids, ears, and skeletal subunits transplant for extensive facial burns in 2015.

Results: Literature review demonstrated that 22 (54%) of the 41 patients undergoing FT received allografts containing periorbital components. Only 14 cases (64%) reported on the presence of ocular and periocular complications. The most common complications consisted of lower eyelid ectropion and lagophthalmos, and nearly all required revisional procedures. Both patients presented with significant periorbital scarring and demonstrated good visual acuity and aesthetic outcomes at postoperative follow up between 6 and 28 months.

Conclusions: Face transplantation can address extensive facial and periorbital disfigurement with satisfactory functional and aesthetic outcomes. The majority of FT performed to date have included periorbital components, and postoperative ocular and periocular complications are common. It is critical for ophthalmologists to play a central role in the care of these patients.

Face transplantation is an effective reconstructive option for patients with extensive facial and periorbital defect with more than half of all procedures to date involving periorbital components, highlighting the critical role of the Ophthalmologist.

*The Hansjörg Wyss Department of Plastic Surgery

Department of Ophthalmology, NYU Langone Health, New York, New York

Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, Tennessee

§Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland

Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida, U.S.A.

Accepted for publication November 7, 2018.

The research was funded by New York University Langone Health, New York City, NY, and a grant from the Office of Naval Research, Arlington, VA (Grant N00014-10-1-0868).

The authors have no financial or conflicts of interest to disclose.

Address correspondence and reprint requests to Eduardo D. Rodriguez, MD, DDS, Hansjörg Wyss Department of Plastic Surgery, NYU Langone Medical Center, 305 E 33rd Street, New York, NY 10016. E-mail: eduardo.rodriguez@nyulangone.org

Face transplantation introduced a paradigm shift in craniofacial reconstruction in 2005,1 and is an effective solution for patients with extensive disfigurement not amenable to conventional reconstruction.2,3 The procedure is complex and relies heavily on multidisciplinary teams with expertise in craniofacial, ocular, reconstructive, and transplant surgery to address all potential reconstructive needs and to ensure optimal postoperative management and outcomes.4,5

Ocular and periocular injuries are frequently encountered in face transplant candidates.2,3 Injury to the globe, eyelids, orbit, and ocular adnexa predispose these patients to eyelid deformities, corneal disease, conjunctival scarring, as well as potential visual impairment and blindness. It is therefore imperative that face transplantation in these patients improves, or at least does not further compromise, periorbital form and function. Furthermore, face transplant teams should be cognizant of potential postoperative complications that may arise, and the ophthalmologist should play an essential role in the surgical and perioperative management of these patients. Of the 41 patients who have undergone face transplantation to date, more than half have received an allograft containing periorbital components.2,3,6 However, a comprehensive assessment of reported ocular and periocular considerations and outcomes has not been performed to date.

The goal of this study was to describe 2 patients who underwent face transplantation including periorbital components, highlight periocular considerations in face transplantation, evaluate reported postoperative ocular complications, and provide a comprehensive update for the ophthalmology community regarding the current state of the field.

Back to Top | Article Outline

METHODS

Patient Population.

Review of clinical data for the 2 face transplant procedures performed by the senior author (E.D.R.) was completed under institutional review board approval (NCT01140087 and NCT02158793), and patient authorizations for release of images and protected health information were obtained.5,7 The first face transplant was performed in 2012, and the second was performed in 2015. This study conforms to the principles outlined in the declaration of Helsinki.

Back to Top | Article Outline

Literature Review.

A comprehensive review of the literature using PubMed was performed to identify all relevant articles between January 1, 2005, and July 1, 2018. The following search terms were used: “face transplantation,” “face allotransplantation,” and “facial vascularized composite allotransplantation.” Article abstracts, text, and references were then screened to identify relevant studies. Non-English articles or those involving nonhuman subjects were excluded. Clinical data were extracted from eligible studies, including patient age, gender, mechanism of injury, facial defect, face transplant date, type of facial allograft, and other relevant available ocular considerations (Table 1). The literature review was performed on July 1, 2018. A total of 258 articles were reviewed, and 46 articles of relevance were included in this study.

TABLE 1

TABLE 1

Back to Top | Article Outline

RESULTS

Among the 41 patients who have undergone face transplantation to date, 22 (54%) have received facial allografts including periorbital components.2,3,5,8–22 Review of the literature showed that only 14 cases (64%) reported on ocular and periocular outcomes, which are reviewed in Table 1.3,5,8–10,12–19 Postoperative complications most frequently affected the eyelids. Lower eyelid ectropion due to horizontal laxity was the most commonly reported eyelid malposition and occurred in 57% of patients (8 of 14),5,9,10,12,14–17,19 and 5 of these patients underwent ectropion repair via canthopexy and canthoplasty.12,14 Four patients (29%) developed unilateral or bilateral lagophthalmos with exposure keratopathy, and 3 patients required corrective surgery.12 Postoperative blepharoptosis was reported in 1 patient who required bilateral levator advancement ptosis repair.12 The authors provide preoperative, perioperative, and postoperative details pertinent to the 2 face transplant procedures performed by the team.

Back to Top | Article Outline

Case 1.

A 37-year-old male sustained a high-energy avulsive ballistic injury to the central face in 1997. The patient had undergone more than 20 reconstructive procedures prior to presentation with suboptimal functional and aesthetic outcomes. On March 19, 2012, he underwent a total face, double jaw, and tongue transplant.7 Preoperative ocular examination revealed best corrected visual acuity of 20/80 OD and 20/25 OS, with normal upper and lower eyelid positions OU and anterior lamellar scarring (Fig. 1). Prior to transplantation, forced eyelid closure showed no lagophthalmos with decent orbicularis function, with impaired blink dynamics OS > OD.18

FIG. 1

FIG. 1

In the donor, supracilliary and subcilliary incisions were made to harvest as much of the anterior lamellae of the upper and lower eyelids as possible, and the deep lateral canthal tissues were also included in the allograft (Fig. 2). Medial canthal tendons were preserved in the donor and recipient. In the recipient, periorbital dissection was performed in a subcutaneous preseptal plane with excision of periorbital scar tissue. The recipient’s orbicularis oculi, tarsus, and retroseptal eyelid structures were all preserved, as was the entirety of the lacrimal drainage apparatus. Coaptations of the facial nerve branches were performed bilaterally, including zygomatic and buccal branches. Particular care was taken to identify and preserve branches to the orbicularis oculi muscle. Nerve coaptations were performed proximally at the level of the nerve arborization. This allowed avoidance of distal dissection, impairment of distal innervation, or disruption of adjacent musculature. Donor supraorbital and infraorbital sensory nerves were laid over their respective sites, as extensive scarring in the recipient prevented identification and direct coaptation of these nerves. Redraping of the eyelid tissue was performed carefully to minimize the risk of ectropion, lagophthalmos, or canthal dystopia, and the allograft lateral canthal tendons were secured 1 mm superior to the level of the medial canthal tendons.7,23

FIG. 2

FIG. 2

Six months following face transplantation, the visual acuity and ocular status remained unchanged compared with preoperatively. Due to brow and forehead ptosis, the patient underwent a bilateral coronal brow lift. Nine months following face transplantation, the patient underwent bilateral lower eyelid blepharoplasty. The patient’s postoperative revisions and clinical course are summarized in Table 2, while the patient’s preoperative, postoperative clinical images, and blink function are demonstrated in Figure 1.18 The patient’s corneal and periocular sensory functions were normal at latest follow up.

TABLE 2

TABLE 2

Back to Top | Article Outline

Case 2.

In 2001, a 41-year-old male firefighter sustained full-thickness thermal burns involving the entire face, scalp, and ears, and underwent multiple skin grafts to the face including periorbital and perioral regions acutely following injury. The patient developed periorbital and perioral contractures resulting in impaired blink dynamics, decreased vision, and oral incompetence (Fig. 3). Conventional reconstruction was deemed inappropriate given the extent of facial disfigurement. Preoperative ocular examination demonstrated best corrected visual acuity of 20/30 OD and 20/60 OS. The intraocular pressures were 12 mm Hg OD and 19 mm Hg OS. External examination was notable for bilateral periocular scarring, as well as lateral and medial tarsorrhaphies with central openings OU. Slit lamp examination revealed signs of chronic exposure keratopathy with a faint corneal scar and superficial punctate keratopathy of the OD. The OS had a moderate central corneal scar extending into the visual axis with neovascularization and diffuse superficial punctate keratopathy. The fundus examination was normal.

FIG. 3

FIG. 3

The patient underwent a total face transplant including the eyelids, ears, and scalp, as well as the nasofrontal, zygomatic, and genial skeletal subunits on August 14, 2015.5 All components of the allograft were procured en bloc, including bilateral full-thickness upper and lower eyelids (Fig. 4).5,24 In the donor, a transconjunctival incision was performed to allow for inclusion of both anterior and posterior lamellae of the upper and lower eyelids in the allograft due to extensive scarring involving the eyelids and conjunctiva in the recipient.5,7,24 In preparation for transplantation, the recipient underwent excision of eyelid scar tissue, including the scarred eyelid margins with part of the tarsus and the preseptal cicatricial tissues. The recipient’s upper tarsus on the upper eyelid and lower tarsus on the lower eyelid were then secured to the corresponding tarsal components on the allograft (Fig. 4). The function of the recipient’s facial nerve branches was found to be intact through nerve stimulation, so coaptations to the allograft nerve branches were not necessary. The allograft’s supraorbital and infraorbital nerves were placed over the appropriate sites in the recipient, as extensive scarring in the recipient prevented identification and coaptation. Meticulous computerized surgical planning and design of a 3-dimensional–printed nasofrontal cutting guide allowed for accurate completion of the nasofrontal osteotomy with preservation of the lacrimal drainage system including the superior and inferior canaliculi, and the medial canthal tendons with their attachments to the naso-orbitoethmoid segments. Careful dissection also allowed preservation of both lateral canthal tendons in the recipient. Final meticulous redraping of the allograft allowed for proper eyelid positioning.

FIG. 4

FIG. 4

Following face transplantation, the patient underwent multiple revisional surgeries summarized in Table 2 to optimize functional and aesthetic outcomes. The first revisional surgery involved bilateral levator advancement for ptosis repair and bilateral lower eyelid ectropion repair on March 2, 2016. On April 12, 2016, the patient underwent a coronal brow lift. On June 8, 2017, due to persistent lower eyelid ectropion, the patient underwent another bilateral lower eyelid ectropion repair. On December 13, 2017, the visual acuity was 20/60 OD and 20/80 OS. Ultimately, the upper eyelid heights were at a normal position with good contour and no evidence of lagophthalmos. Moderate cicatricial ectropion of both lower eyelids persisted with associated exposure keratopathy and stable corneal scarring OU. The lower eyelid ectropion was further exacerbated by significant weight gain in the patient and allograft, which resulted in increased downward traction on the lower eyelids and progressive exposure keratopathy. Corneal and periocular sensory functions were normal at latest follow up. Aggressive topical lubricants were recommended and the patient was referred for corneal subspecialty consultation for a therapeutic bandage contact lens. He was recently fitted with a prosthetic replacement of the ocular surface ecosystem scleral lens device and is demonstrating decreased corneal opacities. Preoperatively, the patient’s blink dynamics were significantly impaired due to extensive periorbital scarring. Postoperatively, there was a significant improvement in both voluntary and involuntary blink dynamics with no significant lagophthalmos with eyelid closure (Fig. 3).

Back to Top | Article Outline

DISCUSSION

Among the 41 patients who have undergone face transplantation to date, 22 (54%) have received facial allografts including periorbital components.2,3,5,8–22 Review of the literature showed that only 14 cases (64%) reported on ocular and periocular outcomes, which are summarized in Table 1.3,5,8–10,12–19 Both patients described in this article required revisional procedures including bilateral brow lift, bilateral upper eyelid ptosis repair, bilateral lower eyelid blepharoplasty, and bilateral lower eyelid ectropion repair. Visual acuity and periocular sensory functions were satisfactory at latest follow up for both patients.

Proper eyelid position and function along with normal tear production are vital to ensure a healthy ocular surface and optimal visual acuity. In face transplant recipients for whom baseline vision was already compromised by the initial facial insult, it is imperative that postoperative periorbital issues be swiftly detected and managed appropriately. Corneal complications can occur due to untreated ectropion or lagophthalmos. Exposure keratopathy, if left untreated, can result in corneal thinning, scarring, ulceration, and perforation, potentially leading to endophthalmitis and corneal blindness. In a study evaluating secondary revisions following face transplantation, tarsorrhaphy was described as the primary treatment for patients presenting with exposure keratopathy, while another patient underwent a bilateral V-Y medial canthus advancement to correct medial canthal malpositioning.12 Importantly, no studies reported or described the role or degree of ophthalmology and oculoplastic surgery involvement in managing these patients.

Complex and composite periorbital defects pose significant reconstructive challenges, particularly when vision is intact. Optimal outcomes depend on proper eyelid-globe apposition, canthal positioning, and tear production and drainage. Periocular reconstruction with attention to form and function are paramount to success in face transplantation. While autologous reconstructive approaches are preferred and can oftentimes achieve these goals, they may require numerous or lengthy procedures, may be limited by autologous donor tissue availability, or may simply be inappropriate for the patient and their respective facial injury.25–27 Vascularized composite allotransplantation offers reconstructive teams an effective method to restore facial and periocular form and function in patients with extensive injuries resulting from burns, blunt, or avulsive trauma, animal attacks, and resection of large neoplastic lesions when autologous reconstructive options are exhausted or incapable of achieving acceptable outcomes.2,3 While revision procedures are frequently necessary to address horizontal eyelid laxity, ectropion, dermatochalasis, ptosis, and brow and forehead ptosis, the functional and aesthetic outcomes that can be achieved with face transplantation are beyond what could be traditionally achieved by autologous reconstruction. Of particular note, transplanting the orbicularis oculi muscle with facial nerve coaptations in the allograft offers the possibility of improved orbicularis oculi function, which is not possible to achieve with autologous grafts or flaps. To date, 41 patients have undergone face transplantation, with 22 patients receiving facial allografts containing periorbital components (Table 1).

Back to Top | Article Outline

Surgical Approach, Clinical Considerations, and Indications.

Surgical approaches for transplanting facial allografts with periorbital components have not been extensively discussed. Complex and composite defects involving periorbital structures are challenging to address and demand equal attention to form and function. Optimal outcomes when reconstructing the periorbital region are best achieved by utilizing best practice techniques from autologous reconstructive efforts that implement craniofacial, microvascular, and aesthetic surgical principles.28 This approach requires preserving periorbital and midfacial contours and reconstructing the skeletal buttresses and overlying soft tissue.29 In patients with extensive facial disfigurement who are not amenable to autologous reconstruction, vascularized composite allotransplantation remains an effective option, relying on attention to the same principles for optimal form and function.5,7 In the 2 face transplants involving periorbital structures detailed in this article, 5 critical reconstructive tenets were followed in an attempt to avoid and minimize postoperative periorbital complications in these procedures. These include preserving the recipient’s medial canthal attachments, avoiding high lateral canthal fixation, ensuring eyelid tissue redundancy in the donor allograft, meticulous preservation of the zygomatic and buccal facial nerve branches, and restoring periorbital sensation when possible.5 The risk of postoperative entropion and ectropion can be minimized by ensuring eyelid tissue redundancy in the donor allograft, which allows subsequent tailoring of the lower eyelid tissue as needed and appropriate tension-free apposition of donor and recipient tissues. Meticulous tissue handling is also of paramount importance to minimize the risk of cicatricial fixation of the lower eyelid.

Facial defects affecting aesthetic and functional units of the midface, eyelids, nose, and lips are particularly difficult to address using conventional reconstructive surgical techniques.27 Local and regional tissues are often affected by the initial injury, which may limit their use and postoperative aesthetic appearance, while microvascular reconstruction using distant tissue may not provide adequate soft tissue thickness or color match. Thermal or electrical facial burns often lead to extensive full-thickness injuries with devastating functional and aesthetic consequences.5,30,31 Resultant eyelid and facial cicatricial contractures from these injuries are extremely challenging to treat and can lead to lagophthalmos, exposure keratopathy, and blindness if not treated appropriately. While no specific guidelines for face transplantation exist, and reconstruction should be tailored to each patient’s disfigurement, defects encompassing the majority of the face along with irreparable damage to the aesthetic and functional units of the central face, including the upper/lower eyelids, nose, or upper/lower lip with or without underlying skeletal craniomaxillofacial deficits, are considered by some groups as indications for face transplantation.25,32,33

Back to Top | Article Outline

Assessment and Contraindications.

Donor shortage is a constant challenge in the field of vascularized composite facial allotransplantation because recipient matching requires immunologic compatibility and appropriate craniofacial dimensions, donor age, skin texture, and color.34–36 Furthermore, face transplant candidates with a history of burns are often immunologically sensitized due to prior transfusions and skin grafts used in their acute management following injury, further complicating donor–recipient matching.37 Patients being considered for face transplantation need to be evaluated by multidisciplinary teams that include surgical and transplant experts, ethicists, psychiatrists, and social workers. Candidates must possess a strong social support system, be psychosocially stable, and be able to comply with lifelong immunosuppression after transplantation.38 As such, active psychological disorders and inadequate social support systems should be considered contraindications to the procedure.39–42 This is particularly important given that many patients evaluated for the procedure are victims of self-inflicted ballistic trauma. Nevertheless, with the exception of 1 patient who ultimately committed suicide, all face transplant recipients following self-inflicted ballistic facial injury have demonstrated encouraging functional and aesthetic outcomes.7,14,43 Face transplantation in blind patients remains a subject of extensive debate.44 Proponents of this approach cite encouraging functional, aesthetic, and psychosocial outcomes. They provide ethical arguments in favor of equitable access to face transplantation in patients with extensive facial disfigurement.17,44–47 Nevertheless, the inability of patients to perceive the resultant outcome or monitor the facial allograft for signs of rejection are important considerations when contemplating this procedure. Some centers consider blindness a contraindication for face transplantation. These considerations are also important in candidates who are sighted but have diminished visual acuity because accelerated cataract formation is highly associated with chronic systemic steroids used for lifelong immunosuppression.48

Both solid organ transplantation and vascularized composite facial allotransplantation can improve quality of life; however, face transplantation is not lifesaving in the same way as solid organ transplantation. Transplant teams have the ethical obligation to weigh the benefits of the procedure with the adverse effects of lifelong immunosuppression including increased risk of malignancies, opportunistic infections, and renal injury.48,49 With these issues in mind, active neoplasms, immunocompromised status, and end-organ dysfunction should be considered contraindications to face transplantation in patients evaluated for extensive facial disfigurement.50

Back to Top | Article Outline

Future Directions.

Facial vascularized composite allotransplantation remains in its early stages, and while the global number of cases performed to date remains limited, results have been encouraging with respect to periocular functional and aesthetic outcomes in partial and total face transplantation. While currently the indications for face transplantation are stringent requiring extensive and devastating facial injuries, as the field continues to progress, the degree and extent of facial injury required to justify this procedure may gradually become less stringent. While none have been performed to date, there is the potential feasibility of performing a more isolated periorbital subunit allotransplantation, which could restore the protective function of the eyelids to the globe, improve sensory innervation to the periorbital region, prevent visual deterioration from exposure keratopathy, and avoid iatrogenic defects associated with autologous reconstruction.51 Interestingly, a novel cadaveric composite eyeball-periorbital transplantation model was recently described.52 The flap was harvested using a “box osteotomy” approach; the allograft pedicle included the facial artery, superficial temporal artery, and external jugular vein with adequate perfusion confirmed through angiography. The optic, oculomotor, trochlear, and abducens nerves were physically included within the allograft. While additional considerations are required to allow for functional extraocular motility or visual transduction, some centers in the United States are currently exploring the possibility of utilizing vascularized composite allotransplantation for sight restoration.52 Similar to other partial and total face transplantation, the benefits of any future periocular vascularized composite transplant must be weighed against the deleterious effects of mandatory lifelong immunosuppression. Further outcomes research focusing on the periocular region in partial and total face transplantation is necessary to characterize outcomes related to facial defects and mechanisms of injury, baseline vision and visual progression, ocular surface complications, sensorimotor function, and effects on quality of life. In the meantime, transplant research efforts are focused on how to minimize immunosuppression and better coordinate the multidisciplinary efforts required for this procedure with close preoperative, intraoperative, and postoperative ophthalmologic involvement. As the field of face transplantation continues to evolve, open reporting of patient outcomes and surgical techniques, including those related to the eye and periocular region, is imperative to developing standardized preoperative and postoperative protocols and pathways.

Back to Top | Article Outline

CONCLUSIONS

Face transplantation is a nascent but effective reconstructive option with encouraging functional and aesthetic outcomes in patients with extensive facial and periorbital defects not amenable to conventional reconstructive techniques. More than half of all face transplants performed to date involved periorbital components, and available data suggest that postoperative ocular and periorbital issues are common with frequent need for revisional procedures. Ophthalmologists and oculoplastic surgeons should be aware of the current state of face transplantation and will hopefully play an increasingly active role in the preoperative, surgical, and postoperative management of face transplant recipients.

Back to Top | Article Outline

REFERENCES

1. Devauchelle B, Badet L, Lengelé B, et al. First human face allograft: early report. Lancet 2006;368:203–9.
2. Khalifian S, Brazio PS, Mohan R, et al. Facial transplantation: the first 9 years. Lancet 2014;384:2153–63.
3. Rifkin WJ, David JA, Plana NM, et al. Achievements and challenges in facial transplantation. Ann Surg 2018;268:260–70.
4. Kantar RS, Rifkin WJ, Diaz-Siso JR, Bernstein GL, Rodriguez ED. Quality improvement in facial transplantation: standard approach for novel procedures. Plast Reconstr Surg Glob Open 2018;6:e1653.
5. Sosin M, Ceradini DJ, Levine JP, et al. Total face, eyelids, ears, scalp, and skeletal subunit transplant: a reconstructive solution for the full face and total scalp burn. Plast Reconstr Surg 2016;138:205–19.
6. Kirkey S. Canada’s First Face Transplant [press release]. National Post 2018. https://nationalpost.com/feature/canadas-first-face-transplant.
7. Dorafshar AH, Bojovic B, Christy MR, et al. Total face, double jaw, and tongue transplantation: an evolutionary concept. Plast Reconstr Surg 2013;131:241–51.
8. Gordon CR, Siemionow M, Papay F, et al. The world’s experience with facial transplantation: what have we learned thus far? Ann Plast Surg 2009;63:572–8.
9. Lantieri L, Meningaud JP, Grimbert P, et al. Repair of the lower and middle parts of the face by composite tissue allotransplantation in a patient with massive plexiform neurofibroma: a 1-year follow-up study. Lancet 2008;372:639–45.
10. Siemionow M, Papay F, Alam D, et al. Near-total human face transplantation for a severely disfigured patient in the USA. Lancet 2009;374:203–9.
11. Meningaud JP, Benjoar MD, Hivelin M, et al. Procurement of total human face graft for allotransplantation: a preclinical study and the first clinical case. Plast Reconstr Surg 2010;126:1181–90.
12. Aycart MA, Alhefzi M, Kueckelhaus M, et al. A retrospective analysis of secondary revisions after face transplantation: assessment of outcomes, safety, and feasibility. Plast Reconstr Surg 2016;138:690e–701e.
13. Barret JP, Gavaldà J, Bueno J, et al. Full face transplant: the first case report. Ann Surg 2011;254:252–6.
14. Lantieri L, Grimbert P, Ortonne N, et al. Face transplant: long-term follow-up and results of a prospective open study. Lancet 2016;388:1398–407.
15. Pomahac B, Pribaz JJ, Bueno EM, et al. Novel surgical technique for full face transplantation. Plast Reconstr Surg 2012;130:549–55.
16. Aycart MA, Perry B, Alhefzi M, et al. Surgical optimization of motor recovery in face transplantation. J Craniofac Surg 2016;27:286–92.
17. Roche NA, Vermeersch HF, Stillaert FB, et al. Complex facial reconstruction by vascularized composite allotransplantation: the first Belgian case. J Plast Reconstr Aesthet Surg 2015;68:362–71.
18. Sosin M, Mundinger GS, Dorafshar AH, et al. Eyelid transplantation: lessons from a total face transplant and the importance of blink. Plast Reconstr Surg 2015;135:167e–175e.
19. Ozkan O, Ozkan O, Ubur M, Hadimioglu N, Cengiz M, Afsar I. Face allotransplantation for various types of facial disfigurements: a series of five cases. Microsurgery 2017 Nov 27. doi: 10.1002/micr.30272.
20. Maciejewski A, Krakowczyk Ł, Szymczyk C, et al. The first immediate face transplant in the world. Ann Surg 2016;263:e36–9.
21. Krakowczyk Ł, Maciejewski A, Szymczyk C, et al. Face transplant in an advanced neurofibromatosis type 1 patient. Ann Transplant 2017;22:53–7.
22. Cleveland Clinic. Woman Receives Total Face Transplant at Cleveland Clinic [press release]. July 18, 2017. https://health.clevelandclinic.org/woman-receives-total-face-transplant-at-cleveland-clinic/.
23. Brown EN, Dorafshar AH, Bojovic B, et al. Total face, double jaw, and tongue transplant simulation: a cadaveric study using computer-assisted techniques. Plast Reconstr Surg 2012;130:815–23.
24. Sosin M, Ceradini DJ, Hazen A, et al. Total face, eyelids, ears, scalp, and skeletal subunit transplant cadaver simulation: the culmination of aesthetic, craniofacial, and microsurgery principles. Plast Reconstr Surg 2016;137:1569–81.
25. Fisher M, Dorafshar A, Bojovic B, Manson PN, Rodriguez ED. The evolution of critical concepts in aesthetic craniofacial microsurgical reconstruction. Plast Reconstr Surg 2012;130:389–98.
26. Haddock NT, Saadeh PB, Siebert JW. Achieving aesthetic results in facial reconstructive microsurgery: planning and executing secondary refinements. Plast Reconstr Surg 2012;130:1236–45.
27. Pribaz JJ, Caterson EJ. Evolution and limitations of conventional autologous reconstruction of the head and neck. J Craniofac Surg 2013;24:99–107.
28. Broyles JM, Abt NB, Shridharani SM, Bojovic B, Rodriguez ED, Dorafshar AH. The fusion of craniofacial reconstruction and microsurgery: a functional and aesthetic approach. Plast Reconstr Surg 2014;134:760–9.
29. Rodriguez ED, Bluebond-Langner R, Park JE, Manson PN. Preservation of contour in periorbital and midfacial craniofacial microsurgery: reconstruction of the soft-tissue elements and skeletal buttresses. Plast Reconstr Surg 2008;121:1738–47.
30. Wainwright DJ. Burn reconstruction: the problems, the techniques, and the applications. Clin Plast Surg 2009;36:687–700.
31. Parrett BM, Pomahac B, Orgill DP, et al. The role of free-tissue transfer for head and neck burn reconstruction. Plast Reconstr Surg 2007;120:1871–8.
32. Mohan R, Borsuk DE, Dorafshar AH, et al. Aesthetic and functional facial transplantation: a classification system and treatment algorithm. Plast Reconstr Surg 2014;133:386–97.
33. Farber SJ, Kantar RS, Diaz-Siso JR, Rodriguez ED. Face transplantation: an update for the United States trauma system. J Craniofac Surg 2018;29:832–8.
34. The Lancet. Organ donation depends on trust. Lancet 2016;387:2575.
35. Aflaki P, Nelson C, Balas B, et al. Simulated central face transplantation: age consideration in matching donors and recipients. J Plast Reconstr Aesthet Surg 2010;63:e283–5.
36. Wallins JS, Chandawarkar AA, Dobry A, et al. Craniofacial measurements of donors and recipients correlate with aesthetic outcome in virtual face transplantation. Plast Reconstr Surg Glob Open 2015;3:e385.
37. Bharadia D, Sinha I, Pomahac B. Role of facial vascularized composite allotransplantation in burn patients. Clin Plast Surg 2017;44:857–64.
38. Bueno EM, Diaz-Siso JR, Pomahac B. A multidisciplinary protocol for face transplantation at Brigham and Women’s Hospital. J Plast Reconstr Aesthet Surg 2011;64:1572–9.
39. Losee JE, Fletcher DR, Gorantla VS. Human facial allotransplantation: patient selection and pertinent considerations. J Craniofac Surg 2012;23:260–4.
40. Jowsey-Gregoire S, Kumnig M. Standardizing psychosocial assessment for vascularized composite allotransplantation. Curr Opin Organ Transplant 2016;21:530–5.
41. Pomahac B, Diaz-Siso JR, Bueno EM. Evolution of indications for facial transplantation. J Plast Reconstr Aesthet Surg 2011;64:1410–6.
42. Siemionow MZ, Gordon CR. Institutional review board-based recommendations for medical institutions pursuing protocol approval for facial transplantation. Plast Reconstr Surg 2010;126:1232–9.
43. Kiwanuka H, Aycart MA, Gitlin DF, et al. The role of face transplantation in the self-inflicted gunshot wound. J Plast Reconstr Aesthet Surg 2016;69:1636–47.
44. Carty MJ, Bueno EM, Lehmann LS, et al. A position paper in support of face transplantation in the blind. Plast Reconstr Surg 2012;130:319–24.
45. Hendrickx H, Blondeel PN, Van Parys H, et al. Facing a new face: an interpretative phenomenological analysis of the experiences of a blind face transplant patient and his partner. J Craniofac Surg 2018;29:826–31.
46. De Letter M, Vanhoutte S, Aerts A, et al. Facial nerve regeneration after facial allotransplantation: a longitudinal clinical and electromyographic follow-up of lip movements during speech. J Plast Reconstr Aesthet Surg 2017;70:729–33.
47. Lemmens GM, Poppe C, Hendrickx H, et al. Facial transplantation in a blind patient: psychologic, marital, and family outcomes at 15 months follow-up. Psychosomatics 2015;56:362–70.
48. Bergmann TK, Barraclough KA, Lee KJ, et al. Clinical pharmacokinetics and pharmacodynamics of prednisolone and prednisone in solid organ transplantation. Clin Pharmacokinet 2012;51:711–41.
49. Nankivell BJ, Borrows RJ, Fung CL, et al. The natural history of chronic allograft nephropathy. N Engl J Med 2003;349:2326–33.
50. Diaz-Siso JR, Sosin M, Plana NM, Rodriguez ED. Face transplantation: complications, implications, and an update for the oncologic surgeon. J Surg Oncol 2016;113:971–5.
51. Sosin M, Mundinger GS, Dorafshar AH, et al. Optimizing reconstruction with periorbital transplantation: clinical indications and anatomic considerations. Plast Reconstr Surg Glob Open 2016;4:e628.
52. Siemionow M, Bozkurt M, Zor F, et al. A new composite eyeball-periorbital transplantation model in humans: an anatomical study in preparation for eyeball transplantation. Plast Reconstr Surg 2018;141:1011–8.
© 2019 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.