Biomaterials for tarsal plate reconstruction and our innovative work

Xing Huang ,Yi Ding ,Lin Lu,Rui Jin,Sun Di,Jun Yang,Xusong Luo

Department of Plastic and Reconstructive Surgery,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China

Keywords:Tarsal plate reconstruction Ear cartilage Preserved sclera Acellular dermal matrix Conjunctival repair Expander capsule

ABSTRACT Large tarsal plate defect reconstruction is one of the most challenging tasks for plastic surgeons.Based on our practical work and literature review,the techniques and postoperative results of the preserved sclera,ear cartilage,and acellular dermal matrix (ADM) as tarsal plate substitutes were investigated.Two cases were reviewed.Case 1 was a 22-year-old female who had total loss of the right lower eyelid.Ear cartilage(23 mm×25 mm)was implanted under the expanded skin during the forehead skin-expanding procedure to form a skin-cartilageexpander capsule compound structure for lower eyelid reconstruction.Case 2 was a 7-year-old boy with a unilateral divided nevus.The lid and conjunctiva of the lower eyelid were invaded.A piece of ADM(12 mm×4 mm)was used to repair the tarsal plate defect (12 mm × 3 mm).The conjunctiva of ADM was covered by itself.An orbicularis oculi myocutaneous flap was used for anterior lamella reconstruction.In case 1,the compound tissue survived and supported the lower eyelid,the lid margin was clear,and the structure was complete over a 1-year follow-up.The aesthetic appearance of the eyelid improved after depilation.It is the first clinical research on the expander capsule as eyelid conjunctiva.In case 2,the conjunctiva completely covered the superior ADM,and the transplant merged with the surrounding tissues without complications after 5 months.The preserved sclera has the longest application history as a tarsal plate substitute.However,it should be preserved in an eye bank and transplanted with conjunctiva repair.Ear cartilage is an autologous tissue that requires conjunctival reconstruction.Our clinical practice was the first to prove the possibility of the expander capsule as eyelid conjunctiva.It is feasible to prefabricate the skin-tarsal conjunctiva complex during the skin expansion procedure.Allogeneic ADM is a common clinical material with advantages of good biological histocompatibility,supportive strength,conjunctivalization,and not requiring donor site surgery.Plastic surgeons are familiar with autologous ear cartilage and ADM,which are easy to obtain and treat.Both ear cartilage and ADM are expected to be the first-line choices in future studies.

1.Introduction

The eyelid is located in front of the eyeball and divides into the anterior lamella(skin and orbicularis oculi muscle)and posterior lamella(tarsal plate and tarsal conjunctiva).1As a supportive structure,the tarsal plate has a curved shape that makes the eyelid closely fit the eyeball during blinking.Histologically,the tarsal plate can be classified as a dense fibrous connective tissue,mainly composed of I/III/IV collagen,chondroitin,and keratan sulfate.These findings suggest that the tarsal plate is a specialized connective tissue that is neither purely fibrous nor cartilaginous.2Part of the levator aponeurosis inserts into a superior tarsal plate to lift the plate when the eyes open.A study in Asians showed that the average height of the upper tarsus is 9.3 mm,whereas that of the lower tarsus is 4.6 mm,and their vertical height ratio is approximately 2.3In addition,dozens of meibomian glands distributed parallel to the tarsal plate are sebaceous glands.The meibomian glands are composed of secretory acini and duct systems that extend throughout the length of the tarsal plate and open on the free lid margin.4The lipids produced by the meibomian glands are the main components of the superficial layer of the tear film.They are helpful against tear evaporation and are beneficial to stabilize the tear film by lowering the surface tension.As a result,dysfunction of the meibomian glands can cause dry eye disease.5

Plate defects caused by trauma,inflammation,tumor,or congenital diseases can be divided into three types -small,moderate,and large defects,based on the area of the lid margin.The techniques of plate reconstruction vary for different degrees of defects.6Small tarsal defects occur in ＜33% of the tarsal plate and are repaired by direct closure.7Moderate defects are defined as those involving 33%-50%of the margin.An adjacent sliding tarsoconjunctival flap from the remaining part of the tarsal plate has been recommended for repair.8,9Large defects involving＞50%of the lid margin are commonly repaired through a Hughes10or a Cutler-Beard11flap procedure.The Hughes flap procedure involves using a modified tarsoconjunctival flap taken from the undersurface of the upper eyelid to repair the lower eyelid defects.The Cutler-Beard bridge flap procedure involves advancing a composite full-thickness lower eyelid flap into the upper eyelid defect by passing it posterior to the remaining lower lid margin.The Hughes or Cutler-Beard flap procedure involves sacrificing the autologous tarsal plate,taking eye closure after one stage,and considering secondary surgery.Thus,large tarsal plate defect reconstruction is one of the most challenging tasks for plastic surgeons in eyelid reconstruction,and seeking a suitable tarsal plate substitute is critical for large defect repair.For natural appearance and function restoration,an ideal tarsal plate should have good biocompatibility,sufficient stiffness,easy accessibility,ease of fabrication,suitable thickness,and increased viability.12Biomaterials involving the preserved sclera,autogenous ear cartilage,and acellular dermal matrix(ADM)are clinically applied.

The literature published from January 2015 to April 2021 was searched in PubMed and Web of Science on the topic of tarsal plate reconstruction using preserved sclera,ear cartilage,or ADM.The search terms used were“preserved sclera”,“allosclera”,“auricular cartilage graft”,“ear cartilage”,“allo dermal matrix”,“xeno dermal matrix”,“acellular dermal matrix”,“tarsal plate defect”,“eyelid reconstruction”,and a combination of these terms.Four articles using preserved sclera,six articles using ear cartilage,and three articles using ADM were identified.The first paper that described ADM for tarsal plate defect repair was published in 2004.However,a total of seven articles on ADM were updated to April 2021.Two cases were finally included in the review.

Fig.1.A woman with total loss of the right lower eyelid.(A)Preoperative view.A 20-mL reinforced expander was implanted in her scalp.(B) The auricular cartilage was taken and placed in the corresponding expander position.(C)The auricular cartilage (white dotted line) was grafted to the original lower eyelid position.The capsule was similar to the surrounding membrane.(D) Aesthetic result after laser depilation without flap thinning.

2.Preserved sclera

The preserved sclera was initially used in the 1950s.13It is widely used in ophthalmologic surgeries but has problems with respect to the inconvenience of source and preservation.In 1980,Wesley et al.14were the first to report a modification of the Cutler-Beard procedure for upper eyelid reconstruction using preserved sclera as a tarsal replacement in 26 patients.All patients were satisfied with the postoperative eyelid appearance without apparent graft absorption or shrinkage.

The sclera is one of the outermost layers of the eyewall that protects the intraocular structure.15It is a lamellar structure mainly made up of connective tissue with few fibroblasts.It has gained popularity owing to its minimum risk of immune reactions or rejection with moderate stiffness and tension.16However,the sclera needs to be preserved in an eye bank.The choroid of the sclera is placed toward the eyeball during transplantation.17The fornix conjunctiva or bulbar conjunctiva was released and transferred as a lining.Additionally,the amniotic membrane is a common material used to repair the conjunctival layer when the remaining conjunctiva is insufficient.18The articles published in the last 5 years are as follows:Kopecky et al.19reported four patients who underwent the Cutler-Beard procedure combined with an eye bank scleral implant to reconstruct extensive full-thickness upper eyelid defects.Hu et al.20used the preserved sclera combined with the fornix conjunctiva to reconstruct the posterior lamella in 24 patients with a large tarsal plate defect after malignant tumor resection.Ding et al.21described 28 patients with abortive cryptophthalmos who underwent upper eyelid and superior fornix reconstruction with a sliding myocutaneous flap and scleral and amniotic grafts;all patients achieved acceptable function and cosmetic outcomes.Noelia et al.22reviewed the clinical application of the sclera over 6 years from 2013 to 2018 in 874 cases.An increasing trend was observed in the use of the sclera during eyelid reconstruction.

3.Autologous ear cartilage

Autologous cartilage is a biomaterial widely used in plastic surgery owing to its abundant source and availability.23It is an elastic cartilage with a spherical surface that offers a proper contour and physical strength.In addition,it is an autologous tissue that has no obvious absorption or rejection.As early as 1997,Yaqub et al.24described the use of autogenous auricular cartilage for correcting upper eyelid entropion in eight patients.Successful repositioning of the eyelid margin without complications,such as upper eyelid ptosis or eyelid retraction,was observed in all patients.

The cartilage was harvested using a posterior approach from the cavity of the auricular concha.The excised auricular cartilage is trimmed into strips to mimic a normal tarsal plate and repair the defect.25,26However,the ear cartilage lacks a mucous layer.Common methods to reconstruct the conjunctiva layer to protect the cornea involve fornix conjunctiva or oral mucosa transplantation.

Different types of modified methods using ear cartilage have been proposed and discussed recently.Several articles published in the last 5 years have been presented,focusing on ear cartilage usage and conjunctival reconstruction.Yang et al.27used an auricular cartilage graft combined with a superficial temporal artery island flap to reconstruct full-thickness lower eyelid defects in six patients.A local flap was turned over as a lining to substitute the conjunctiva.The length of the transplanted cartilage was the same as the lid margin,and it was fixed to the periosteum of the orbital bone.Salil et al.28described a modified Cutler-Beard procedure using autogenous ear cartilage for tarsal plate reconstruction in 16 patients whose defects were ≥70%.The lower tarsal plate was preserved.The remaining conjunctiva of the upper eyelid and transplanted conjunctiva were sutured together as a lining.Naoto et al.29reported full-thickness eyelid defect reconstruction using the oral mucosa and ear cartilage in 13 patients.They advised that the ear cartilage should be sufficient to interpose the defect to provide sufficient support rather than entirely cover the defect.Riri et al.30used ear cartilage with perichondrium (as lining) for the posterior lamella and a rectangular advancement flap for the anterior lamella in four patients with adequate excess skin around small to medium eyelid defects.Zhen et al.31described the use of a π-shaped auricular cartilage composed of three cartilage strips(one horizontal and two vertical strips connected at three equal points)to reconstruct the posterior lamella of the lower eyelid.The width of the horizontal strip was the same as the height of the lower tarsal plate.The fornix conjunctiva was released as a lining.Lucian et al.32described a new technique for placing a cartilage graft between the subcutaneous and musculoaponeurotic layers of a paramedian forehead flap to reconstruct full-thickness defects involving approximately 80% of the lower eyelid in a 60-year-old Caucasian woman.All the abovementioned studies reported good esthetics and functional results,with no infections,cartilage exposure,eyelid ptosis,or eyelid retraction noted in any patient.

Wieslander et al.33used the expander capsule as a substitute to reconstruct lower eyelid defects in six pigs,and all reconstructions were successful.Gu et al.34implanted tissue expanders into 66 rabbits and placed a chondro-perichondrial graft harvested from the auricular concha on the edge of the tissue expander.The sandwich-prefabricated advancement flaps were used to reconstruct the entire upper eyelid defect.The studies revealed that the long-term capsule had a normal conjunctiva-like appearance without edema,infection,corneal damage,or necrosis.

Based on previous experimental studies,we reconstructed a right lower eyelid tarsal plate in a 22-year-old female patient with total loss of the lower eyelid caused by trauma (Fig.1).The forehead skin flap was pre-extended,and a 23 cm × 25 mm ear cartilage graft was inserted under the expanded skin to form a skin-ear cartilage-expander capsule that constitutes a structure for lower eyelid reconstruction.The expander capsule was used as a substitute for the conjunctiva.The patient was followed up after 1 year.The compound tissue survived and supported the lower eyelid,the lid margin was clear,and the structure was complete.Eye irritation caused by friction or hardness of the cartilage was not observed.No lagophthalmos or eyelid retraction was observed.After laser depilation,the appearance of the lower eyelid significantly improved.Flap thinning was conducted 2 years later.The cartilage wasin situwithout absorption,and the capsule was not obviously contracted because of the supportive structure.Although the conjunctiva biopsy was deficient to protect the patient,conjunctiva crawling replacement was estimated to occur based on previous animal experiments and our observations.This is the first known clinical case of full-thickness eyelid reconstruction using ear cartilage combined with expander capsules.

4.Acellular dermal matrix

ADM is widely used to treat wound cover,abdominal wall reconstruction,and breast reconstruction.35-38The clinical value of tarsal plate substitutes is also gaining increased attention.39ADM is an acellular collagen matrix obtained from the skin,porcine dermis,and bovine ligament of fresh human corpses and is composed of basement membrane and dermal layer.The antigenic components in normal skin are removed using different methods to achieve immunologic inertia.40The basement membrane is a natural matrix for epithelial cell migration,in which conjunctival epithelial cells can recover the graft surface within 2-3 weeks after surgery.41Thus,conjunctival reconstruction is unnecessary in tarsal reconstruction using ADM with unparalleled advantages.

Additionally,ADM provides adequate support to maintain eyelid appearance as a scaffold.ADM can induce fibroblasts and capillaries to grow orderly and integrate well with adjacent tissues.42In recent years,the manufacturing technique of commercial ADM products has been continuously processed to reduce antigenicity and improve stiffness.43

Fig.2.Lower eyelid reconstruction using allogenic ADM.(A) Preoperative view.(B)Lid margin invasion.(C) Lesion removal.(D) Allogenic ADM repaired the tarsal plate defect without conjunctiva transplant.(E) Intraoperative view.(F-G) Postoperative views after 5 months.The reconstructed tarsal plate was exhibited with manual traction,and no eyelid ectropion was observed.

The earliest international literature on tarsal plate reconstruction using ADM was published in 1999.44Allogeneic ADM without a mucous layer was used to prolong the original tarsal plate to strengthen supportive function in patients with lower eyelid retraction.A systematic review of the available literature was conducted using PubMed and Web of Science.We included references that described the use of ADM as a tarsal plate substitute in eyelid reconstruction.The search terms used were as follows:allo dermal matrix,xeno dermal matrix,acellular dermal matrix,tarsal plate defect,eyelid reconstruction,and combinations of these terms.Studies that used ADM for tarsal plate defect repairin situwere included,whereas experimental studies and studies on lower eyelid retraction correction and using a wrap for orbital implants were excluded.The literature search was screened,and seven articles were identified with relevant manuscripts for review.

In 2005,the Zhongshan Ophthalmic Center conducted the first research on allogeneic ADM application for tarsal plate defect reconstructionsin situin 10 patients.The basement membrane was placed toward the eyelid conjunctiva and the dermis layer toward the orbicularis oculi muscle for blood supply.The conjunctiva was repaired using the fornix conjunctiva and amniotic membrane as supplement.Ten cases healed without severe complications or evident eyelid edema.45This group performed a series of clinical studies.They reported 14 cases using allogeneic ADM for tarsal plate reconstruction after excision of cicatricial tarsal tissue to correct eyelid entropion in 2009.46The conjunctiva layer retained its self-healing property and was observed to cover ADM after 2 months.One study described a new technique using a composite graft of allogeneic ADM and split-thickness buccal mucosa to repair the posterior lamella of full-thickness upper eyelid defects caused by burns or trauma in eight patients in 2012.47The orbicularis and free skin flaps were released to reconstruct the anterior lamella.All transplants survived,and the reconstructed upper eyelid moved as usual.No lagophthalmos or other complications were observed.In 2010,one patient in the Department of Ophthalmology,Mayo Clinic,had squamous cell carcinoma involving the entire upper eyelid.A human dermal matrix graft was used to recreate the tarsus.ADM survived,and the eyelid appearance improved.48

The number of articles using an ADM to reconstruct tarsal plates has increased in the last 5 years.Vahdani et al.49reported a retrospective study of acellular dermal allograft as a tarsal substitute in the reconstruction of extensive eyelid defects,including five patients with an average follow-up of 84.3 months.The posterior lamella of eyelid defects was replaced directly by ADM without the mucosal layer,whereas theanterior lamella was repaired using a myocutaneous flap.The conjunctiva was observed on the ADM surface.The function and appearance of the eyelid were greatly re-established.Kyu et al.50described a sandwich(lower eyelid tarsoconjunctival flap-ADM-musculocutaneous flap) technique to reconstruct the upper eyelid due to relatively insufficient lower eyelid tissue.ADM was trimmed in the same way as the defect for strengthening the posterior lamella.Philip et al.51described 13 patients who underwent marginal defect repair with a porcine dermal matrix graft sandwiched between a myocutaneous flap and a conjunctival flap.The outcomes in all patients mentioned above were favorable without functional and aesthetic problems,and no complications related to ADM transplantation were observed.

Our team reconstructed a lower eyelid tarsal plate in a 7-year-old boy with a divided nevus using allogeneic ADM (Fig.2).The lesion in the lower eyelid (12 mm × 11 mm) was entirely excised,which caused a 12 mm × 3 mm tarsal plate defect.A trimmed allogeneic ADM(12 mm×4 mm)was used to reconstruct the defectin situ.The basement membrane was placed toward the eyeball without conjunctiva repair.A skin-orbicularis muscle flap (incisional design as Tenzel flap incision)was released to cover ADM for anterior lamella reconstruction.After 5 months,the conjunctiva completely covered the superior ADM,and the transplant merged with the surrounding tissues with no eyelid ectropion observed.The patient and his parents were satisfied with the functional and aesthetic results,without complaints of unsuitable sensations or complications.

Overall,the ADM used as a tarsal substitute can easily be obtained with good sources.It is a supportive structure that maintains eyelid stability and also exhibits good biocompatibility.In addition,autologous donor site surgery and donor-site-related complications can be avoided,and the operation time can be shortened.Most importantly,both function and appearance achieve satisfactory results.However,ADM has not been widely used in the field of tarsal plate defect reconstruction,and combining it with conjunctiva reconstruction has not reached a consensus.The pieces of literature mentioned in this chapter were classified according to the conjunctiva transplant,as shown in Table 1.ADM has advantages such as abundant source and easy operation without donor site surgery compared with autologous ear cartilage and preserved sclera.As a result,ADM has wide application prospects in tarsal plate defect reconstruction.

Table 1 The classification of conjunctiva transplantation in tarsal plate reconstruction using ADM.

5.Conclusion

Currently,there is no unified standard for the biomaterials chosen for eyelid reconstruction.Common tarsal substitutes,including ear cartilage and preserved sclera,are widely used in clinical practice.With the development of material-producing techniques,the clinical application of ADM is gaining more and more attention.

The preserved sclera has the longest application history as a tarsal plate substitute.However,it needs to be preserved in an eye bank and transplanted in combination with conjunctiva repair.Ear cartilage is an autologous tissue that plastic surgeons are familiar with but requires additional donor site surgery and conjunctiva reconstruction.ADM has advantages such as abundant sources and convenient preservation and does not need unnecessary donor site surgery.Given the insufficient clinical literature and scientific research,some problems have not been clearly explained,including whether ADM transplantation should be combined with conjunctiva reconstruction and how to choose the epithelization method,vascularization and inflammatory reaction in the process of ADM modification,long-term stability and contracture possibility of ADM,and incidence of postoperative dry eyes.In short,the clinical application value of ADM requires further long-term follow-up results and in-depth research.

Ethics declarations

Ethics approval and consent to participate

The need for ethics approval was waived given the nature of the report.All participants provided written informed consent prior to study enrollment.

Consent for publication

All the patients included in this research gave written informed consent to publish the data contained within this study.

Competing interest

The authors declare that they have no competing interests.

Authors’ contributions

Huang X:Writing-Original Draft,Data curation,Formal analysis.Ding Y:Writing-Original Draft,Software,Validation.Lu L:Methodology,Data curation.Jin R:Investigation,Resources.Di S:Investigation.Yang J:Project administration.Luo X:Conceptualization,Supervision,Writing-Reviewing and Editing.

Acknowledgements

This study was supported by the Shanghai Committee of Science and Technology,China(grant no.19ZR1430100).