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Bioengineered Acellular Dermal Matrix Spacer Grafts for Lower Eyelid Retraction Repair
Ophthalmic Technology Assessment
Bioengineered Acellular Dermal Matrix Spacer Grafts for Lower Eyelid Retraction Repair A Report by the American Academy of Ophthalmology Jeremiah P. Tao, MD,1 Vinay K. Aakalu, MD, MPH,2 Edward J. Wladis, MD,3 Rachel K. Sobel, MD,4 Suzanne K. Freitag, MD,5 Jill A. Foster, MD,6 Michael T. Yen, MD7 Purpose: To review the literature on the efficacy and safety of bioengineered acellular dermal matrix (BADM) grafts for lower eyelid retraction repair. Methods: A literature search was conducted in the PubMed database initially in January 2018 and updated in July 2019 to identify all studies in the English language literature on the use of BADM grafts in eyelid reconstruction. The searches yielded 193 citations, and 15 of the 34 articles selected for full review met all inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study. Two of the 15 studies included were rated level II and 13 were rated level III. Results: The definition of success varied, but lower eyelid position improvement using lower lid margin-topupillary reflex distance was the most common outcome measure. Other end points were the amount of lagophthalmos, cosmesis, exposure, reoperation, or complications, as well as prosthesis retention in anophthalmic socket cases. The surgeon-reported success rate of these outcomes ranged from 75% to 100%. Minor complications included cyst formation, infection, chemosis, pyogenic granuloma, and corneal abrasion. No serious complications such as blindness, anaphylactic reaction, or terminal disease transmission occurred. Of the 526 implants included for assessment in these disparate studies, 27 cases (5%) required reoperation. Conclusions: No level I evidence was available, and the existing level II and level III studies have variable primary end points, study design limitations, and only short-term follow-up data. The current literature suggests that BADM grafts represent an implantation option for lower eyelid retraction repair. Short-term results are favorable, and the materials used may fill an important gap in care for patients for whom no acceptable alternatives exist, but long-term safety and efficacy remain unknown. Ophthalmology 2019;-:1e7 ª 2019 by the American Academy of Ophthalmology
The American Academy of Ophthalmology prepares Ophthalmic Technology Assessments to evaluate new and existing procedures, drugs, and diagnostic and screening tests. The goal of an Ophthalmic Technology Assessment is to review systematically the available research for clinical efficacy and safety. After review by members of the Ophthalmic Technology Assessment Committee, other Academy committees, relevant subspecialty societies, and legal counsel, assessments are submitted to the Academy’s Board of Trustees for consideration as official Academy statements. The purpose of this assessment by the Ophthalmic Technology Assessment Committee Oculoplastics and Orbit Panel was to review the published literature on the efficacy and safety of bioengineered acellular dermal matrix (BADM) grafts for lower eyelid retraction repair.
ª 2019 by the American Academy of Ophthalmology Published by Elsevier Inc.
Background Lower eyelid retraction is a common condition that can occur for a number of reasons including a complication of blepharoplasty and other facial cosmetic surgery, after trauma or tumor resection, as a congenital anomaly, as well as in association with thyroid eye disease (TED) or negative vector facial morphologic features. Ocular irritation, foreign body sensation, blurred vision, and epiphora are common symptoms. Permanent vision loss is possible in severe cases as a result of corneal exposure and decompensation. Posterior lamellar eyelid scarring, eyelid tissue loss, involutional eyelid changes, or TED may be indications for a spacer graft. Surgeons have used a variety of materials in the lower eyelid. Scleral grafts once were favored, but their
https://doi.org/10.1016/j.ophtha.2019.11.011 ISSN 0161-6420/19
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Ophthalmology Volume -, Number -, Month 2019 use may be limited because of degradation, shrinkage, and concern for rejection and transmission of pathogens, including prions. Fascia allografts lack the necessary rigidity for lower eyelid retraction correction. Other autologous options include hard palate, cartilage (i.e., ear, nasal, or rib), and dermis or fat composite grafts. Size, thickness, shape, pliability, and structural constraints as well as donor site morbidity may limit the use of autografts. Synthetic devices are available; however, integration may be limited, and the material may be prone to extrusion or foreign body reaction. In recent decades, BADM materials have been developed to address a variety of soft tissue conditions. Applications include reconstructive surgery of the breast, abdominal wall, and extremities and for other indications within the head and neck.1 The purported advantages include the predictable rigidity profile, the ability to customize (sculpt) to the desired size and configuration, the ability to suture directly to the implant, and the possibility that the wound-healing response could be enhanced because of the biologic collagen framework that theoretically brings glycosaminoglycans, fibronectin, and other basic wound-healing units to the field.1 Importantly, these products also avoid a second surgical donor site and the associated morbidity. Although other allografts and xenografts also circumvent donor site morbidity, BADM materials are devoid of cells and purportedly have less rejection risk.1 This Ophthalmic Technology Assessment reviewed the safety and efficacy of these various acellular dermal devices (allografts or xenografts) for lower eyelid retraction repair.
Questions for Assessment The focus of this assessment is to address the following question: Are the currently available BADM spacer grafts safe and effective for use in surgical repair of lower eyelid retraction?
Description of Evidence A literature search was conducted in the PubMed database initially in January 2018 and updated in July 2019. Only articles that assessed the use of a BADM spacer graft for the treatment of lower eyelid retraction in humans were included. The search strategy used the following search terms: eyelid spacer, spacer graft, eyelid graft, ENDURAGen, collagen matrix graft, collagen implant, AlloDerm, dermal matrix graft, bioengineered graft, TarSys, eyelid retraction, eyelid implant, porcine acellular dermal matrix graft, bovine dermal matrix graft, SurgiMend, human acellular dermal matrix graft, xenograft, allograft, and human acellular dermis. The searches identified 193 potentially relevant articles. Thirty-four were selected for full-text review, and 15 met all inclusion criteria for this assessment. The panel methodologist (V.K.A.) assigned a level of evidence to each of the included articles based on a rating scale developed by the Oxford Centre for Evidence-Based Medicine.2 A level I rating was assigned to well-designed and well-conducted randomized clinical trials; a level II rating was assigned to
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well-designed case-control and cohort studies and lowerquality randomized studies; and a level III rating was assigned to case series, case reports, and lower-quality cohort and case-control studies. Two studies met level II criteria and 13 studies met level III criteria. There were no level I studies.
Published Results A summary of the 15 studies with abstracted lower eyelid retraction repair data is provided in Table 1. Level II Study Outcomes In a prospective, randomized trial, Barmettler and Heo3 compared outcomes of lower eyelid retraction repair in 3 study groups, each using a different type of BADM spacer graft material or autologous ear cartilage grafts. The authors included a variety of causes for lower eyelid retraction including cicatricial, paralytic, and negative vector causes. The bioengineered devices were bovine acellular dermal matrix (SurgiMend; Integra, Plainsboro, NJ; n ¼ 11) and porcine acellular dermal matrix (ENDURAGen; Stryker, Kalamazoo, MI; n ¼ 12). The ear cartilage group included 19 eyelids. Although the study had no control group, at 6 months, the lower lid margin-to-pupillary reflex distance (MRD2) improved in all groups and was not statistically significantly different among the 3 study groups (2.4-mm improvement for cartilage, 1.8-mm improvement for bovine BADM, and 2.5-mm improvement for porcine BADM; P ¼ 0.27). No serious complications were reported, and minor adverse events were similar between groups. In a nonrandomized study of 54 TED patients, Kim et al4 retrospectively investigated the surgical outcome of lower eyelid retractor recession with and without a human BADM graft (AlloDerm; LifeCell Corporation, Woodlands, TX) during a swinging lower eyelid approach (lateral canthotomy and inferior cantholysis) for orbital decompression. Patients receiving decompression were divided into 3 groups: group 1 with conjunctiva lengthening using human BADM (36 eyes), group 2 with inferior retractor recession (33 eyes), and group 3 with decompression only (26 eyes). The study was not powered to detect differences among the 3 groups, and groups were not matched for the primary outcome. At the 4- to 6month postoperative visit, mean improvements in MRD2 as well as postoperative improvement in inferior scleral show were significantly higher with the use of the BADM compared with retractor recession alone (P < 0.001) or orbit decompression alone (P < 0.001). The authors did not report serious complications. Level III Study Outcomes Bee et al5 reported a retrospective case series of 84 patients who underwent surgical procedures using human BADM (AlloDerm). The study comprised a wide range of applications that also included reconstruction after malignancy resection (n ¼ 26), trauma (n ¼ 19), resection
Table 1. Summary of Included Studies
Author (Year)
Level of Evidence
Barmettler and Heo (2018)3
II
Kim et al (2017)4
Type of Bioengineered Acellular Dermal Matrix
Lower Eyelid Retraction Vector
Canthoplasty Adjuncts
No. of Eyelids
TED
Orbit decompression
36
Bee et al (2015)5
III
Human (AlloDerm)
Cicatricial (including anophthalmic)
NR
54 (18 contracted socket)
Borelli et al (2012)15
III
Porcine (TarSys)
Cicatricial and paralytic
NR
1
Grumbine et al (2019)17
III
Porcine (ENDURAGen)
Cicatricial
NR
10
Jiaqi et al (2006)6
III
Human (ReDerm)
Cicatricial
NR
Kim et al (2014)16
III
Porcine (TarSys)
NR
Lee et al (2010)7
III
Human (AlloDerm and DermaMatrix)
Prophylaxis during blepharoplasty in TED patient Cicatricial (including anophthalmic) paralytic, and negative vector
15 (includes upper eyelid) 2
NR
12 (9 paralytic, TED, facial abnormality, 3 contracted sockets)
Li et al (2005)8
III
Human (AlloDerm)
Cicatricial (after blepharoplasty)
Midface lift
70
Liao and Wei (2013)9
III
Porcine (TarSys)
TED
NR
37
McCord et al (2008)10
III
Porcine (ENDURAGen)
Cicatricial or negative vector
Scruggs et al (2015)11
III
Human (Belladerm)
131 lower eyelid (17 as lateral canthal reinforcement) 15
Shorr et al (2000)12
III
Human (AlloDerm)
Involutional, cicatricial, and paralytic Cicatricial and TED
Most with midface lift, 17 with lateral graft only NR Midface lift
92
MRD2 improvement or need for reoperation MRD2 improvement
9/11 (82%; bovine) and 8/12 (75%; porcine) MRD2 improvement > with spacer than retractor recession or just decompression 92.8% favorable (includes nonlower eyelid) Exposure and lagophthalmos improved MRD2 improvement (2 required additional surgery) 100% satisfactory
>6
Functional or cosmetic improvement Ocular surface exposure and lagophthalmos MRD2 improvement or need for reoperation Function and cosmesis Cystlike mass, bilateral Improvement in symptoms, prosthesis retention, additional surgery MRD2 (compared with hard palate) MRD2, lagophthalmos, cosmesis, complications Complications MRD2 Clinical improvement or complications
Cystlike mass, bilateral
>4
>2 3 >6 >4 3
10/13 (77%) successful (3 required additional surgery)
>3
Improved MRD2 and equivalent to hard palate (100%) Improved MRD2, 100% satisfactory cosmetic result
>4
9 cases with need for revision, 4 cases of infection (92%) 15/15 (100%) with improvement in MRD2 89 (97%; 3 cases required reoperation)
NR
>6
>3 >6
(Continued)
Ophthalmic Technology Assessment
11 bovine, 12 porcine
Follow-up (mos)
NR
Results
Tao et al
Cicatricial, paralytic, and negative
II
Bovine (Surgimed) and porcine (ENDURAGen) Human (AlloDerm)
Outcome Measure
3
4
>3
>6
57% contraction (vs. 16% for hard palate) 16/21 (76%) had improved MRD2 Contraction percent compared with hard palate MRD2 III Taban et al (2005)14
Human (AlloDerm)
Human (AlloDerm) III Sullivan and Dailey (2003)13
MRD2 ¼ lower lid margin-to-pupillary reflex distance; NR ¼ not reported; TED ¼ thyroid eye disease.
21 Midface lift
7 Most with midface lift
Cicatricial (includes anophthalmic), TED, and paralytic Cicatricial (after blepharoplasty)
Canthoplasty Adjuncts Level of Evidence Author (Year)
Type of Bioengineered Acellular Dermal Matrix
Lower Eyelid Retraction Vector
Table 1. (Continued.)
No. of Eyelids
Outcome Measure
Results
Follow-up (mos)
Ophthalmology Volume -, Number -, Month 2019 after congenital lesion (n ¼ 15), and involutional change (n ¼ 11). Fifty-four lower eyelid retraction repair procedures were included. Of these, 18 were in the setting of an anophthalmic socket. Other applications were for scar repair or to provide patch grafts or filler. The mean duration of follow-up was 530 days (minimum, 2 months; maximum not reported). Overall, 93% of patients achieved favorable outcomes. According to the report, surgical outcomes were categorized as favorable, moderate, and poor satisfaction with regard to functional improvement, cosmesis, or both. No implant rejection or serious adverse events were reported. Jiaqi et al6 reported a retrospective case series of eyelid reconstruction using human BADM (ReDerm; Jieya, Beijing, China) in 15 eyelids of 13 patients that included 5 patients with thermal burns and 8 patients with chemical burns. The device was implanted between the inferior edge of the remaining tarsus and recessed retractor band. At a mean follow-up of 9 months, “satisfactory function and cosmesis were obtained.” The authors reported no implant rejection or serious adverse events. Lee et al7 reported a retrospective case series of eyelid implantation of human BADM (DermaMatrix; Synthes, West Chester, PA). Nine lower eyelids demonstrated retraction resulting from facial palsy, TED, or a craniofacial abnormality. Three lower eyelids were present in the setting of a contracted anophthalmic socket and an inability to retain a prostheses. At 3 months after surgery, they reported an overall 77% success rate (which included 1 patient with BADM used in the upper eyelid after cancer resection) as denoted by improved symptoms. Three patients underwent further surgery. One of these reoperations was in a patient with lower eyelid retraction on upgaze that likely was the result of aberrant nerve regeneration. The authors did not report implant rejection or serious adverse events. Li et al8 retrospectively compared bioengineered human BADM (AlloDerm) with hard palate autografts in patients also undergoing midface lifting for lower eyelid retraction after blepharoplasty. Thirty-five patients undergoing human BADM were compared with 25 patients undergoing hard palate grafting. Patients were not randomized. Both groups showed improvement in MRD2 at a minimum follow-up of 4 months. No statistically significant difference was found in the amount of eyelid elevation between the human BADM and hard palate groups (P ¼ 0.121). No implant rejection or serious adverse events were reported. Liao and Wei9 retrospectively reviewed patients with TED who underwent lower eyelid retraction surgery using porcine BADM eyelid spacer grafts (TarSys; IOP Ophthalmics, Costa Mesa, CA). Outcome measures included MRD2, reduction of lagophthalmos, cosmetic appearance, complications, and need for further surgery. Six months after surgery, the authors reported statistically significant differences between preoperative and postoperative MRD2 and lagophthalmos (P < 0.0001). They reported no implant rejection or serious adverse events. McCord et al10 retrospectively reviewed their experience with porcine BADM (ENDURAGen; Tissue Science
Tao et al
Ophthalmic Technology Assessment
Laboratories, Aldershot, United Kingdom; distributed in the United States by Porex Surgical, Newnan, GA) for eyelid retraction resulting from cicatricial or negative vectors. One hundred four lower eyelids were treated using graft material. The graft was used for lateral canthal reinforcement in an additional 17 eyelids. Their report included 8 grafts implanted to the upper eyelid. The authors described 13 eyelid complications, but they did not report how many of these involved the lower eyelid. The complications included 4 undercorrections requiring additional spacer graft, 4 infections, 3 oversized spacers requiring trimming, and 2 cases requiring an additional autograft not further specified. All 4 cases of infection were treated successfully with oral and topical antibiotics. Follow-up time was not reported, and the authors reported no implant rejection or other adverse events. In a prospective, nonrandomized noncomparative study, Scruggs et al11 described the use of human BADM harvested from live donors (BellaDerm; Musculoskeletal Transplant Foundation, Edison, NJ) as a posterior spacer graft to correct symptomatic lower eyelid retraction secondary to involutional, cicatricial, and paralytic causes. With an average follow-up duration of 15.6 months (range, 3e34 months), the mean improvement in MRD2 for all eyelids after surgery was 2.2 mm (P < 0.0001). They reported no implant rejection or serious adverse events. In a retrospective, noncomparative case series, Shorr et al12 described the use of human BADM grafts (AlloDerm) as a posterior lamella eyelid spacer graft in 92 cases (52 patients) comprising lower eyelid retraction after blepharoplasty in 86 cases (49 patients) and TED in 6 cases (3 patients). The follow-up was 6 months. Inferior scleral show was eliminated in 89 eyelids. Three eyelids required a second similar operation with another human BADM to correct the inferior scleral show. The authors reported no serious complications attributable to the BADM material. Sullivan and Dailey13 reported on a comparison of human BADM (AlloDerm) with hard palate autografts. Seven lower eyelids of 4 patients received BADM and 6 lower eyelids of 4 patients received hard palate grafts. All of the patients with lower eyelid retraction also underwent an endoscopic subperiosteal midface lift. At a follow-up of at least 6 months, the eyelids were everted, and the grafts were measured using a stainless-steel ruler. The authors reported that human BADM contracts significantly (P < 0.005) more than hard palate mucosa when used as a lower eyelid spacer graft. All BADM implants were a success based on 2 criteria: (1) improved exposure symptoms and (2) resolution of lower eyelid retraction. No implant rejection or serious adverse events were reported. Taban et al14 retrospectively analyzed patients who underwent lower eyelid reconstruction with subperiosteal midface lifting, middle lamellae scar lysis, and placement of lower eyelid human BADM (AlloDerm) graft. Analysis included 21 surgical procedures in 11 patients. All patients had undergone at least 1 previous lower eyelid surgery with resultant lower eyelid retraction and scleral show. Of 21 procedures, 16 (8 of 11 patients) demonstrated improvement of lower eyelid position. The mean
improvement of the MRD at an average follow-up of 215 days was 1.6 mm (range, 0.4e2.2 mm). Of 21 procedures, 5 (3 patients) failed to result in improvement in lower eyelid position, with the mean eyelid position lower after surgery by 0.8 mm (range, 0.4e1.4 mm). Borelli et al15 reported a single retrospective case of successful correction of severe eyelid retraction resulting from cicatricial and paralytic vectors using porcine BADM (TarSys). The graft was sewn into the posterior lamella through a subciliary incision and a concomitant lateral canthoplasty was performed with no implant rejection or serious adverse events. The follow-up time was 3 months. Kim et al16 reported a retrospective case of inflammatory cysts with a foreign body reaction in both lower eyelids 3 months after implantation of porcine BADM (TarSys) during blepharoplasty as prophylaxis of bilateral lower eyelid retraction in a patient with TED. Grumbine et al17 reported a retrospective analysis of patients (10 eyelids in 9 patients) who underwent lower eyelid retraction repair with placement of porcine acellular dermal matrix using an en glove technique (ENDURAGen; Stryker, Kalamazoo, MI). All patients showed improvement in MRD2. The mean improvement in MRD2 was 1.9 mm (range, 1e3.5 mm) at a mean follow-up of 8.5 months (range, 6e13 months). Two complications, including scrolling of the collagen implant within the subconjunctival pocket and another case of lateral canthal dystopia, were each managed successfully with a minor surgical intervention. The surgical technique for lower eyelid implantation was similar across reports and included a lateral canthoplasty with graft placement to the posterior lamella and inferior to the tarsus. Adjunctive major procedures were variable and included midface lift or orbit decompression. One variation was a subset of patients (17/121) in McCord et al10 who demonstrated lateral canthal tissue loss. A BADM graft was sewn in to the middle lamella of the lateral eyelid and to periosteal tissues at the lateral rim as well to support the lateral canthus. Methodologies for measuring success and failure differed among the studies included in this assessment, and the studies did not adhere to a single, standardized scoring system. Improvement in MRD2 was the most common outcome measure. The amount of lagophthalmos, cosmesis, exposure, reoperation, prosthesis retention in anophthalmic socket cases, or complications were other end points. The author-defined success rates for these various outcomes ranged from 75% to 100%. A few reported complications included cyst formation, chemosis, infection, pyogenic granuloma, aberrant nerve regeneration, and corneal abrasion. No serious complication such as blindness, anaphylactic reaction, or untreatable disease transmission was identified. Of the 526 BADM eyelid implants abstracted from the disparate studies, 27 (5%) underwent reoperation. The studies described various types of BADM implants. Most reports addressed human-derived grafts (AlloDerm, DermaMatrix, Belladerm, and ReDerm). Porcine BADM (ENDURAGen or TarSys) was described less often, and bovine-derived graft (SurgiMend) use was described in only 1 study.
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Ophthalmology Volume -, Number -, Month 2019 The underlying causes of lower eyelid retraction were heterogeneous and included cicatricial, involutional, paralytic, and negative vector lower eyelid position (e.g., prominent globe in TED or a shallow orbit). In select cases, the grafts were used for reconstruction after malignancy resection, congenital defects, or, in 1 case, as eyelid retraction prophylaxis during concomitant lower eyelid blepharoplasty. In addition, ancillary surgical procedures were highly variable between and even within many reports. For lower eyelid retraction, adjunctive surgical interventions included lateral tarsal strip, tarsorrhaphy, midface lift, and orbit decompression.
infection. No clear consensus exists regarding whether one BADM graft material is clearly more effective than the others. Only Barmettler and Heo3 investigated more than 1 type of BADM, and they reported similar efficacy between bovine and porcine BADM grafts. In conclusion, the current literature suggests that BADM represents an implantation option for eyelid retraction repair. Although short-term results are favorable and these materials may fill an important gap in care for patients for whom no acceptable alternatives exist, insufficient data are available in the literature to conclude that BADM grafts are safe and effective in the long term.
Conclusions
Future Research
Bioengineered acellular dermal matrix implants may be helpful for the treatment of lower eyelid retraction, yet more rigorous clinical research with carefully defined outcome measures obtained after longer-term follow-up are indicated. This oculofacial application may add new indications to a variety of other more established uses, including breast and abdominal reconstructions.1 In general, use of a BADM may be helpful in clinical scenarios that require additional soft tissue support and where autologous options are inadequate or where harvest morbidity is objectionable. All eyelid allografts and xenografts are at risk of transmission for disease. However, BADM grafts are processed to remove cellular components from human, porcine, and bovine dermis and theoretically to reduce the risk for disease transmission.1 Human tissue is screened for HIV and hepatitis. Another theoretical advantage of BADM is that it retains connective tissue components that offer structural support with less concern for rejection. In addition, tissue ingrowth may be improved compared with synthetic materials, and grafts eventually may be either fully integrated or fully replaced with recipient tissues.1 Bioengineered acellular dermal matrix implants provide a convenient off-the-shelf alternative that obviates second surgical site morbidity. The literature remains incomplete and further studies are warranted, especially those with long-term follow-up data. The studies included in this report were mostly retrospective and only 3 were prospective.3,11,13 None of the studies was controlled. Most studies provided varying and inconsistent quantitative measurements, yet most included an analysis of MRD2 based on either clinical examination photographs, quantitative measurements, or both. Other outcomes included lagophthalmos, scleral show, ocular surface findings, cosmesis, complications, prosthesis retention in anophthalmic socket cases, and a need for reoperation. The follow-up duration in these studies typically was several months after implantation, and no studies reported long-term (years) data. In these short-term studies, patient-reported outcomes generally were favorable, with a minority of patients demonstrating minor complications that included cyst formation, corneal abrasions, pyogenic granuloma, chemosis, inflammation, aberrant nerve regeneration, and mild
Prospective, controlled, comparative studies (preferably randomized clinical trials) comparing BADM grafts with other standard implants or no implant are needed. Moreover, consensus metrics for success and detailed phenotyping and matching of study participants also are needed. This Ophthalmic Technology Assessment uncovered reconstructive uses of BADM grafts for indications other than lower eyelid retraction repair, such as upper eyelid retraction repair, anophthalmic socket rehabilitation, and reconstruction after tumor resection. Assessment for efficacy for these indications is warranted. Long-term follow-up is important because prion and other disease transmissions remain a concern, and detection is elusive and may occur after decades of latency. Finally, technology continues to evolve, and new materials or manufacturing techniques may supplant current BADMs.
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References 1. Fosnot J, Kovach 3rd SJ, Serletti JM. Acellular dermal matrix: general principles for the plastic surgeon. Aesthet Surg J. 2011;31(7 Suppl):5Se12S. 2. Oxford Centre for Evidence-Based Medicine. Levels of evidence (March 2009). http://www.cebm.net/index.aspx?o¼1025. Accessed 02.06.17. 3. Barmettler A, Heo M. A prospective, randomized comparison of lower eyelid retraction repair with autologous auricular cartilage, bovine acellular dermal matrix (SurgiMend), and porcine acellular dermal matrix (ENDURAGen) spacer grafts. Ophthalmic Plast Reconstr Surg. 2018;34(3):266e273. 4. Kim KY, Woo YJ, Jang SY, et al. Correction of lower eyelid retraction using acellular human dermis during orbital decompression. Ophthalmic Plast Reconstr Surg. 2017;33(3): 168e172. 5. Bee YS, Alonzo B, Ng JD. Review of AlloDerm acellular human dermis regenerative tissue matrix in multiple types of oculofacial plastic and reconstructive surgery. Ophthalmic Plast Reconstr Surg. 2015;31(5):348e351. 6. Jiaqi C, Zheng W, Jianjun G. Eyelid reconstruction with acellular human dermal allograft after chemical and thermal burns. Burns. 2006;32(2):208e211. 7. Lee EW, Berbos Z, Zaldivar RA, et al. Use of DermaMatrix graft in oculoplastic surgery. Ophthalmic Plast Reconstr Surg. 2010;26(3):153e154.
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8. Li TG, Shorr N, Goldberg RA. Comparison of the efficacy of hard palate grafts with acellular human dermis grafts in lower eyelid surgery. Plast Reconstr Surg. 2005;116(3):873e878. discussion 879e880. 9. Liao SL, Wei YH. Correction of lower lid retraction using TarSys bioengineered grafts for Graves ophthalmopathy. Am J Ophthalmol. 2013;156(2), 387e392 e381. 10. McCord C, Nahai FR, Codner MA, et al. Use of porcine acellular dermal matrix (ENDURAGen) grafts in eyelids: a review of 69 patients and 129 eyelids. Plast Reconstr Surg. 2008;122(4):1206e1213. 11. Scruggs JT, McGwin Jr G, Morgenstern KE. Use of (BellaDerm) in lower eyelid retraction repair. Ophthalmic Plast Reconstr Surg. 2015;31(5):379e384. 12. Shorr N, Perry JD, Goldberg RA, et al. The safety and applications of acellular human dermal allograft in ophthalmic plastic and reconstructive surgery: a preliminary report. Ophthalmic Plast Reconstr Surg. 2000;16(3):223e230.
13. Sullivan SA, Dailey RA. Graft contraction: a comparison of acellular dermis versus hard palate mucosa in lower eyelid surgery. Ophthalmic Plast Reconstr Surg. 2003;19(1): 14e24. 14. Taban M, Douglas R, Li T, et al. Efficacy of “thick” acellular human dermis (AlloDerm) for lower eyelid reconstruction: comparison with hard palate and thin AlloDerm grafts. Arch Facial Plast Surg. 2005;7(1):38e44. 15. Borrelli M, Unterlauft J, Kleinsasser N, Geerling G. Decellularized porcine derived membrane (TarSys(R)) for correction of lower eyelid retraction. Orbit. 2012;31(3):187e189. 16. Kim HJ, Grossniklaus HE, Wojno TH. A cyst-like foreign body reaction to porcine decellularized membrane (TarSys). Ophthalmic Plast Reconstr Surg. 2014;30(4):e100ee102. 17. Grumbine FL, Idowu O, Kersten RC, et al. Correction of lower eyelid retraction with en glove placement of porcine dermal collagen matrix implant. Plast Reconstr Surg. 2019;143(3): 743e746.
Footnotes and Financial Disclosures Originally received: November 14, 2019. Final revision: November 15, 2019. Accepted: November 15, 2019. Available online: ---.
V.K.A.: Consultant e Horizon Therapeutics, Lake Forest, IL (US Operations). Manuscript no. D-19-00734.
1
Gavin Herbert Eye Institute, University of California, Irvine School of Medicine, Irvine, California.
2
Illinois Eye and Ear Infirmary, University of Illinois College of Medicine at Chicago, Chicago, Illinois. 3
Ophthalmic Plastic Surgery, Lions Eye Institute, Department of Ophthalmology, Albany Medical Center, Albany (Slingerlands), New York.
4
Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
5
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
6
Ophthalmic Surgeons and Consultants of Ohio, Columbus, Ohio.
7
Cullen Eye Institute, Baylor College of Medicine, Houston, Texas. Financial Disclosure(s): The author(s) have made the following disclosure(s): J.P.T.: Consultant e Horizon Therapeutics, Lake Forest, IL (US Operations).
E.J.W.: Consultant e Valeant Pharmaceuticals, Bridgewater, NJ; Consultant e Horizon Therapeutics, Lake Forest, IL; Equity Owner e Praxis Biotechnology, Sacramento, CA. S.K.F.: Consultant e Horizon Therapeutics, Lake Forest, IL (US Operations). Funded without commercial support by the American Academy of Ophthalmology. HUMAN SUBJECTS: No human subjects were included in this study. No animal subjects were included in this study. Prepared by the Ophthalmic Technology Assessment Committee Oculoplastics and Orbit Panel and approved by the American Academy of Ophthalmology’s Board of Trustees Month October 11, 2019. Abbreviations and Acronyms: BADM ¼ bioengineered acellular dermal matrix; MRD2 ¼ lower lid margin-to-pupillary reflex distance; TED ¼ thyroid eye disease. Correspondence: Ali Al-Rajhi, PhD, MPH, American Academy of Ophthalmology, Quality and Data Science, P. O. Box 7424, San Francisco, CA 94120-7424. E-mail: [email protected].
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Bioengineered Acellular Dermal Matrix Spacer Grafts for Lower Eyelid Retraction Repair A Report by the American Academy of Ophthalmology Jeremiah P. Tao, MD,1 Vinay K. Aakalu, MD, MPH,2 Edward J. Wladis, MD,3 Rachel K. Sobel, MD,4 Suzanne K. Freitag, MD,5 Jill A. Foster, MD,6 Michael T. Yen, MD7 Purpose: To review the literature on the efficacy and safety of bioengineered acellular dermal matrix (BADM) grafts for lower eyelid retraction repair. Methods: A literature search was conducted in the PubMed database initially in January 2018 and updated in July 2019 to identify all studies in the English language literature on the use of BADM grafts in eyelid reconstruction. The searches yielded 193 citations, and 15 of the 34 articles selected for full review met all inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study. Two of the 15 studies included were rated level II and 13 were rated level III. Results: The definition of success varied, but lower eyelid position improvement using lower lid margin-topupillary reflex distance was the most common outcome measure. Other end points were the amount of lagophthalmos, cosmesis, exposure, reoperation, or complications, as well as prosthesis retention in anophthalmic socket cases. The surgeon-reported success rate of these outcomes ranged from 75% to 100%. Minor complications included cyst formation, infection, chemosis, pyogenic granuloma, and corneal abrasion. No serious complications such as blindness, anaphylactic reaction, or terminal disease transmission occurred. Of the 526 implants included for assessment in these disparate studies, 27 cases (5%) required reoperation. Conclusions: No level I evidence was available, and the existing level II and level III studies have variable primary end points, study design limitations, and only short-term follow-up data. The current literature suggests that BADM grafts represent an implantation option for lower eyelid retraction repair. Short-term results are favorable, and the materials used may fill an important gap in care for patients for whom no acceptable alternatives exist, but long-term safety and efficacy remain unknown. Ophthalmology 2019;-:1e7 ª 2019 by the American Academy of Ophthalmology
The American Academy of Ophthalmology prepares Ophthalmic Technology Assessments to evaluate new and existing procedures, drugs, and diagnostic and screening tests. The goal of an Ophthalmic Technology Assessment is to review systematically the available research for clinical efficacy and safety. After review by members of the Ophthalmic Technology Assessment Committee, other Academy committees, relevant subspecialty societies, and legal counsel, assessments are submitted to the Academy’s Board of Trustees for consideration as official Academy statements. The purpose of this assessment by the Ophthalmic Technology Assessment Committee Oculoplastics and Orbit Panel was to review the published literature on the efficacy and safety of bioengineered acellular dermal matrix (BADM) grafts for lower eyelid retraction repair.
ª 2019 by the American Academy of Ophthalmology Published by Elsevier Inc.
Background Lower eyelid retraction is a common condition that can occur for a number of reasons including a complication of blepharoplasty and other facial cosmetic surgery, after trauma or tumor resection, as a congenital anomaly, as well as in association with thyroid eye disease (TED) or negative vector facial morphologic features. Ocular irritation, foreign body sensation, blurred vision, and epiphora are common symptoms. Permanent vision loss is possible in severe cases as a result of corneal exposure and decompensation. Posterior lamellar eyelid scarring, eyelid tissue loss, involutional eyelid changes, or TED may be indications for a spacer graft. Surgeons have used a variety of materials in the lower eyelid. Scleral grafts once were favored, but their
https://doi.org/10.1016/j.ophtha.2019.11.011 ISSN 0161-6420/19
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Ophthalmology Volume -, Number -, Month 2019 use may be limited because of degradation, shrinkage, and concern for rejection and transmission of pathogens, including prions. Fascia allografts lack the necessary rigidity for lower eyelid retraction correction. Other autologous options include hard palate, cartilage (i.e., ear, nasal, or rib), and dermis or fat composite grafts. Size, thickness, shape, pliability, and structural constraints as well as donor site morbidity may limit the use of autografts. Synthetic devices are available; however, integration may be limited, and the material may be prone to extrusion or foreign body reaction. In recent decades, BADM materials have been developed to address a variety of soft tissue conditions. Applications include reconstructive surgery of the breast, abdominal wall, and extremities and for other indications within the head and neck.1 The purported advantages include the predictable rigidity profile, the ability to customize (sculpt) to the desired size and configuration, the ability to suture directly to the implant, and the possibility that the wound-healing response could be enhanced because of the biologic collagen framework that theoretically brings glycosaminoglycans, fibronectin, and other basic wound-healing units to the field.1 Importantly, these products also avoid a second surgical donor site and the associated morbidity. Although other allografts and xenografts also circumvent donor site morbidity, BADM materials are devoid of cells and purportedly have less rejection risk.1 This Ophthalmic Technology Assessment reviewed the safety and efficacy of these various acellular dermal devices (allografts or xenografts) for lower eyelid retraction repair.
Questions for Assessment The focus of this assessment is to address the following question: Are the currently available BADM spacer grafts safe and effective for use in surgical repair of lower eyelid retraction?
Description of Evidence A literature search was conducted in the PubMed database initially in January 2018 and updated in July 2019. Only articles that assessed the use of a BADM spacer graft for the treatment of lower eyelid retraction in humans were included. The search strategy used the following search terms: eyelid spacer, spacer graft, eyelid graft, ENDURAGen, collagen matrix graft, collagen implant, AlloDerm, dermal matrix graft, bioengineered graft, TarSys, eyelid retraction, eyelid implant, porcine acellular dermal matrix graft, bovine dermal matrix graft, SurgiMend, human acellular dermal matrix graft, xenograft, allograft, and human acellular dermis. The searches identified 193 potentially relevant articles. Thirty-four were selected for full-text review, and 15 met all inclusion criteria for this assessment. The panel methodologist (V.K.A.) assigned a level of evidence to each of the included articles based on a rating scale developed by the Oxford Centre for Evidence-Based Medicine.2 A level I rating was assigned to well-designed and well-conducted randomized clinical trials; a level II rating was assigned to
2
well-designed case-control and cohort studies and lowerquality randomized studies; and a level III rating was assigned to case series, case reports, and lower-quality cohort and case-control studies. Two studies met level II criteria and 13 studies met level III criteria. There were no level I studies.
Published Results A summary of the 15 studies with abstracted lower eyelid retraction repair data is provided in Table 1. Level II Study Outcomes In a prospective, randomized trial, Barmettler and Heo3 compared outcomes of lower eyelid retraction repair in 3 study groups, each using a different type of BADM spacer graft material or autologous ear cartilage grafts. The authors included a variety of causes for lower eyelid retraction including cicatricial, paralytic, and negative vector causes. The bioengineered devices were bovine acellular dermal matrix (SurgiMend; Integra, Plainsboro, NJ; n ¼ 11) and porcine acellular dermal matrix (ENDURAGen; Stryker, Kalamazoo, MI; n ¼ 12). The ear cartilage group included 19 eyelids. Although the study had no control group, at 6 months, the lower lid margin-to-pupillary reflex distance (MRD2) improved in all groups and was not statistically significantly different among the 3 study groups (2.4-mm improvement for cartilage, 1.8-mm improvement for bovine BADM, and 2.5-mm improvement for porcine BADM; P ¼ 0.27). No serious complications were reported, and minor adverse events were similar between groups. In a nonrandomized study of 54 TED patients, Kim et al4 retrospectively investigated the surgical outcome of lower eyelid retractor recession with and without a human BADM graft (AlloDerm; LifeCell Corporation, Woodlands, TX) during a swinging lower eyelid approach (lateral canthotomy and inferior cantholysis) for orbital decompression. Patients receiving decompression were divided into 3 groups: group 1 with conjunctiva lengthening using human BADM (36 eyes), group 2 with inferior retractor recession (33 eyes), and group 3 with decompression only (26 eyes). The study was not powered to detect differences among the 3 groups, and groups were not matched for the primary outcome. At the 4- to 6month postoperative visit, mean improvements in MRD2 as well as postoperative improvement in inferior scleral show were significantly higher with the use of the BADM compared with retractor recession alone (P < 0.001) or orbit decompression alone (P < 0.001). The authors did not report serious complications. Level III Study Outcomes Bee et al5 reported a retrospective case series of 84 patients who underwent surgical procedures using human BADM (AlloDerm). The study comprised a wide range of applications that also included reconstruction after malignancy resection (n ¼ 26), trauma (n ¼ 19), resection
Table 1. Summary of Included Studies
Author (Year)
Level of Evidence
Barmettler and Heo (2018)3
II
Kim et al (2017)4
Type of Bioengineered Acellular Dermal Matrix
Lower Eyelid Retraction Vector
Canthoplasty Adjuncts
No. of Eyelids
TED
Orbit decompression
36
Bee et al (2015)5
III
Human (AlloDerm)
Cicatricial (including anophthalmic)
NR
54 (18 contracted socket)
Borelli et al (2012)15
III
Porcine (TarSys)
Cicatricial and paralytic
NR
1
Grumbine et al (2019)17
III
Porcine (ENDURAGen)
Cicatricial
NR
10
Jiaqi et al (2006)6
III
Human (ReDerm)
Cicatricial
NR
Kim et al (2014)16
III
Porcine (TarSys)
NR
Lee et al (2010)7
III
Human (AlloDerm and DermaMatrix)
Prophylaxis during blepharoplasty in TED patient Cicatricial (including anophthalmic) paralytic, and negative vector
15 (includes upper eyelid) 2
NR
12 (9 paralytic, TED, facial abnormality, 3 contracted sockets)
Li et al (2005)8
III
Human (AlloDerm)
Cicatricial (after blepharoplasty)
Midface lift
70
Liao and Wei (2013)9
III
Porcine (TarSys)
TED
NR
37
McCord et al (2008)10
III
Porcine (ENDURAGen)
Cicatricial or negative vector
Scruggs et al (2015)11
III
Human (Belladerm)
131 lower eyelid (17 as lateral canthal reinforcement) 15
Shorr et al (2000)12
III
Human (AlloDerm)
Involutional, cicatricial, and paralytic Cicatricial and TED
Most with midface lift, 17 with lateral graft only NR Midface lift
92
MRD2 improvement or need for reoperation MRD2 improvement
9/11 (82%; bovine) and 8/12 (75%; porcine) MRD2 improvement > with spacer than retractor recession or just decompression 92.8% favorable (includes nonlower eyelid) Exposure and lagophthalmos improved MRD2 improvement (2 required additional surgery) 100% satisfactory
>6
Functional or cosmetic improvement Ocular surface exposure and lagophthalmos MRD2 improvement or need for reoperation Function and cosmesis Cystlike mass, bilateral Improvement in symptoms, prosthesis retention, additional surgery MRD2 (compared with hard palate) MRD2, lagophthalmos, cosmesis, complications Complications MRD2 Clinical improvement or complications
Cystlike mass, bilateral
>4
>2 3 >6 >4 3
10/13 (77%) successful (3 required additional surgery)
>3
Improved MRD2 and equivalent to hard palate (100%) Improved MRD2, 100% satisfactory cosmetic result
>4
9 cases with need for revision, 4 cases of infection (92%) 15/15 (100%) with improvement in MRD2 89 (97%; 3 cases required reoperation)
NR
>6
>3 >6
(Continued)
Ophthalmic Technology Assessment
11 bovine, 12 porcine
Follow-up (mos)
NR
Results
Tao et al
Cicatricial, paralytic, and negative
II
Bovine (Surgimed) and porcine (ENDURAGen) Human (AlloDerm)
Outcome Measure
3
4
>3
>6
57% contraction (vs. 16% for hard palate) 16/21 (76%) had improved MRD2 Contraction percent compared with hard palate MRD2 III Taban et al (2005)14
Human (AlloDerm)
Human (AlloDerm) III Sullivan and Dailey (2003)13
MRD2 ¼ lower lid margin-to-pupillary reflex distance; NR ¼ not reported; TED ¼ thyroid eye disease.
21 Midface lift
7 Most with midface lift
Cicatricial (includes anophthalmic), TED, and paralytic Cicatricial (after blepharoplasty)
Canthoplasty Adjuncts Level of Evidence Author (Year)
Type of Bioengineered Acellular Dermal Matrix
Lower Eyelid Retraction Vector
Table 1. (Continued.)
No. of Eyelids
Outcome Measure
Results
Follow-up (mos)
Ophthalmology Volume -, Number -, Month 2019 after congenital lesion (n ¼ 15), and involutional change (n ¼ 11). Fifty-four lower eyelid retraction repair procedures were included. Of these, 18 were in the setting of an anophthalmic socket. Other applications were for scar repair or to provide patch grafts or filler. The mean duration of follow-up was 530 days (minimum, 2 months; maximum not reported). Overall, 93% of patients achieved favorable outcomes. According to the report, surgical outcomes were categorized as favorable, moderate, and poor satisfaction with regard to functional improvement, cosmesis, or both. No implant rejection or serious adverse events were reported. Jiaqi et al6 reported a retrospective case series of eyelid reconstruction using human BADM (ReDerm; Jieya, Beijing, China) in 15 eyelids of 13 patients that included 5 patients with thermal burns and 8 patients with chemical burns. The device was implanted between the inferior edge of the remaining tarsus and recessed retractor band. At a mean follow-up of 9 months, “satisfactory function and cosmesis were obtained.” The authors reported no implant rejection or serious adverse events. Lee et al7 reported a retrospective case series of eyelid implantation of human BADM (DermaMatrix; Synthes, West Chester, PA). Nine lower eyelids demonstrated retraction resulting from facial palsy, TED, or a craniofacial abnormality. Three lower eyelids were present in the setting of a contracted anophthalmic socket and an inability to retain a prostheses. At 3 months after surgery, they reported an overall 77% success rate (which included 1 patient with BADM used in the upper eyelid after cancer resection) as denoted by improved symptoms. Three patients underwent further surgery. One of these reoperations was in a patient with lower eyelid retraction on upgaze that likely was the result of aberrant nerve regeneration. The authors did not report implant rejection or serious adverse events. Li et al8 retrospectively compared bioengineered human BADM (AlloDerm) with hard palate autografts in patients also undergoing midface lifting for lower eyelid retraction after blepharoplasty. Thirty-five patients undergoing human BADM were compared with 25 patients undergoing hard palate grafting. Patients were not randomized. Both groups showed improvement in MRD2 at a minimum follow-up of 4 months. No statistically significant difference was found in the amount of eyelid elevation between the human BADM and hard palate groups (P ¼ 0.121). No implant rejection or serious adverse events were reported. Liao and Wei9 retrospectively reviewed patients with TED who underwent lower eyelid retraction surgery using porcine BADM eyelid spacer grafts (TarSys; IOP Ophthalmics, Costa Mesa, CA). Outcome measures included MRD2, reduction of lagophthalmos, cosmetic appearance, complications, and need for further surgery. Six months after surgery, the authors reported statistically significant differences between preoperative and postoperative MRD2 and lagophthalmos (P < 0.0001). They reported no implant rejection or serious adverse events. McCord et al10 retrospectively reviewed their experience with porcine BADM (ENDURAGen; Tissue Science
Tao et al
Ophthalmic Technology Assessment
Laboratories, Aldershot, United Kingdom; distributed in the United States by Porex Surgical, Newnan, GA) for eyelid retraction resulting from cicatricial or negative vectors. One hundred four lower eyelids were treated using graft material. The graft was used for lateral canthal reinforcement in an additional 17 eyelids. Their report included 8 grafts implanted to the upper eyelid. The authors described 13 eyelid complications, but they did not report how many of these involved the lower eyelid. The complications included 4 undercorrections requiring additional spacer graft, 4 infections, 3 oversized spacers requiring trimming, and 2 cases requiring an additional autograft not further specified. All 4 cases of infection were treated successfully with oral and topical antibiotics. Follow-up time was not reported, and the authors reported no implant rejection or other adverse events. In a prospective, nonrandomized noncomparative study, Scruggs et al11 described the use of human BADM harvested from live donors (BellaDerm; Musculoskeletal Transplant Foundation, Edison, NJ) as a posterior spacer graft to correct symptomatic lower eyelid retraction secondary to involutional, cicatricial, and paralytic causes. With an average follow-up duration of 15.6 months (range, 3e34 months), the mean improvement in MRD2 for all eyelids after surgery was 2.2 mm (P < 0.0001). They reported no implant rejection or serious adverse events. In a retrospective, noncomparative case series, Shorr et al12 described the use of human BADM grafts (AlloDerm) as a posterior lamella eyelid spacer graft in 92 cases (52 patients) comprising lower eyelid retraction after blepharoplasty in 86 cases (49 patients) and TED in 6 cases (3 patients). The follow-up was 6 months. Inferior scleral show was eliminated in 89 eyelids. Three eyelids required a second similar operation with another human BADM to correct the inferior scleral show. The authors reported no serious complications attributable to the BADM material. Sullivan and Dailey13 reported on a comparison of human BADM (AlloDerm) with hard palate autografts. Seven lower eyelids of 4 patients received BADM and 6 lower eyelids of 4 patients received hard palate grafts. All of the patients with lower eyelid retraction also underwent an endoscopic subperiosteal midface lift. At a follow-up of at least 6 months, the eyelids were everted, and the grafts were measured using a stainless-steel ruler. The authors reported that human BADM contracts significantly (P < 0.005) more than hard palate mucosa when used as a lower eyelid spacer graft. All BADM implants were a success based on 2 criteria: (1) improved exposure symptoms and (2) resolution of lower eyelid retraction. No implant rejection or serious adverse events were reported. Taban et al14 retrospectively analyzed patients who underwent lower eyelid reconstruction with subperiosteal midface lifting, middle lamellae scar lysis, and placement of lower eyelid human BADM (AlloDerm) graft. Analysis included 21 surgical procedures in 11 patients. All patients had undergone at least 1 previous lower eyelid surgery with resultant lower eyelid retraction and scleral show. Of 21 procedures, 16 (8 of 11 patients) demonstrated improvement of lower eyelid position. The mean
improvement of the MRD at an average follow-up of 215 days was 1.6 mm (range, 0.4e2.2 mm). Of 21 procedures, 5 (3 patients) failed to result in improvement in lower eyelid position, with the mean eyelid position lower after surgery by 0.8 mm (range, 0.4e1.4 mm). Borelli et al15 reported a single retrospective case of successful correction of severe eyelid retraction resulting from cicatricial and paralytic vectors using porcine BADM (TarSys). The graft was sewn into the posterior lamella through a subciliary incision and a concomitant lateral canthoplasty was performed with no implant rejection or serious adverse events. The follow-up time was 3 months. Kim et al16 reported a retrospective case of inflammatory cysts with a foreign body reaction in both lower eyelids 3 months after implantation of porcine BADM (TarSys) during blepharoplasty as prophylaxis of bilateral lower eyelid retraction in a patient with TED. Grumbine et al17 reported a retrospective analysis of patients (10 eyelids in 9 patients) who underwent lower eyelid retraction repair with placement of porcine acellular dermal matrix using an en glove technique (ENDURAGen; Stryker, Kalamazoo, MI). All patients showed improvement in MRD2. The mean improvement in MRD2 was 1.9 mm (range, 1e3.5 mm) at a mean follow-up of 8.5 months (range, 6e13 months). Two complications, including scrolling of the collagen implant within the subconjunctival pocket and another case of lateral canthal dystopia, were each managed successfully with a minor surgical intervention. The surgical technique for lower eyelid implantation was similar across reports and included a lateral canthoplasty with graft placement to the posterior lamella and inferior to the tarsus. Adjunctive major procedures were variable and included midface lift or orbit decompression. One variation was a subset of patients (17/121) in McCord et al10 who demonstrated lateral canthal tissue loss. A BADM graft was sewn in to the middle lamella of the lateral eyelid and to periosteal tissues at the lateral rim as well to support the lateral canthus. Methodologies for measuring success and failure differed among the studies included in this assessment, and the studies did not adhere to a single, standardized scoring system. Improvement in MRD2 was the most common outcome measure. The amount of lagophthalmos, cosmesis, exposure, reoperation, prosthesis retention in anophthalmic socket cases, or complications were other end points. The author-defined success rates for these various outcomes ranged from 75% to 100%. A few reported complications included cyst formation, chemosis, infection, pyogenic granuloma, aberrant nerve regeneration, and corneal abrasion. No serious complication such as blindness, anaphylactic reaction, or untreatable disease transmission was identified. Of the 526 BADM eyelid implants abstracted from the disparate studies, 27 (5%) underwent reoperation. The studies described various types of BADM implants. Most reports addressed human-derived grafts (AlloDerm, DermaMatrix, Belladerm, and ReDerm). Porcine BADM (ENDURAGen or TarSys) was described less often, and bovine-derived graft (SurgiMend) use was described in only 1 study.
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Ophthalmology Volume -, Number -, Month 2019 The underlying causes of lower eyelid retraction were heterogeneous and included cicatricial, involutional, paralytic, and negative vector lower eyelid position (e.g., prominent globe in TED or a shallow orbit). In select cases, the grafts were used for reconstruction after malignancy resection, congenital defects, or, in 1 case, as eyelid retraction prophylaxis during concomitant lower eyelid blepharoplasty. In addition, ancillary surgical procedures were highly variable between and even within many reports. For lower eyelid retraction, adjunctive surgical interventions included lateral tarsal strip, tarsorrhaphy, midface lift, and orbit decompression.
infection. No clear consensus exists regarding whether one BADM graft material is clearly more effective than the others. Only Barmettler and Heo3 investigated more than 1 type of BADM, and they reported similar efficacy between bovine and porcine BADM grafts. In conclusion, the current literature suggests that BADM represents an implantation option for eyelid retraction repair. Although short-term results are favorable and these materials may fill an important gap in care for patients for whom no acceptable alternatives exist, insufficient data are available in the literature to conclude that BADM grafts are safe and effective in the long term.
Conclusions
Future Research
Bioengineered acellular dermal matrix implants may be helpful for the treatment of lower eyelid retraction, yet more rigorous clinical research with carefully defined outcome measures obtained after longer-term follow-up are indicated. This oculofacial application may add new indications to a variety of other more established uses, including breast and abdominal reconstructions.1 In general, use of a BADM may be helpful in clinical scenarios that require additional soft tissue support and where autologous options are inadequate or where harvest morbidity is objectionable. All eyelid allografts and xenografts are at risk of transmission for disease. However, BADM grafts are processed to remove cellular components from human, porcine, and bovine dermis and theoretically to reduce the risk for disease transmission.1 Human tissue is screened for HIV and hepatitis. Another theoretical advantage of BADM is that it retains connective tissue components that offer structural support with less concern for rejection. In addition, tissue ingrowth may be improved compared with synthetic materials, and grafts eventually may be either fully integrated or fully replaced with recipient tissues.1 Bioengineered acellular dermal matrix implants provide a convenient off-the-shelf alternative that obviates second surgical site morbidity. The literature remains incomplete and further studies are warranted, especially those with long-term follow-up data. The studies included in this report were mostly retrospective and only 3 were prospective.3,11,13 None of the studies was controlled. Most studies provided varying and inconsistent quantitative measurements, yet most included an analysis of MRD2 based on either clinical examination photographs, quantitative measurements, or both. Other outcomes included lagophthalmos, scleral show, ocular surface findings, cosmesis, complications, prosthesis retention in anophthalmic socket cases, and a need for reoperation. The follow-up duration in these studies typically was several months after implantation, and no studies reported long-term (years) data. In these short-term studies, patient-reported outcomes generally were favorable, with a minority of patients demonstrating minor complications that included cyst formation, corneal abrasions, pyogenic granuloma, chemosis, inflammation, aberrant nerve regeneration, and mild
Prospective, controlled, comparative studies (preferably randomized clinical trials) comparing BADM grafts with other standard implants or no implant are needed. Moreover, consensus metrics for success and detailed phenotyping and matching of study participants also are needed. This Ophthalmic Technology Assessment uncovered reconstructive uses of BADM grafts for indications other than lower eyelid retraction repair, such as upper eyelid retraction repair, anophthalmic socket rehabilitation, and reconstruction after tumor resection. Assessment for efficacy for these indications is warranted. Long-term follow-up is important because prion and other disease transmissions remain a concern, and detection is elusive and may occur after decades of latency. Finally, technology continues to evolve, and new materials or manufacturing techniques may supplant current BADMs.
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References 1. Fosnot J, Kovach 3rd SJ, Serletti JM. Acellular dermal matrix: general principles for the plastic surgeon. Aesthet Surg J. 2011;31(7 Suppl):5Se12S. 2. Oxford Centre for Evidence-Based Medicine. Levels of evidence (March 2009). http://www.cebm.net/index.aspx?o¼1025. Accessed 02.06.17. 3. Barmettler A, Heo M. A prospective, randomized comparison of lower eyelid retraction repair with autologous auricular cartilage, bovine acellular dermal matrix (SurgiMend), and porcine acellular dermal matrix (ENDURAGen) spacer grafts. Ophthalmic Plast Reconstr Surg. 2018;34(3):266e273. 4. Kim KY, Woo YJ, Jang SY, et al. Correction of lower eyelid retraction using acellular human dermis during orbital decompression. Ophthalmic Plast Reconstr Surg. 2017;33(3): 168e172. 5. Bee YS, Alonzo B, Ng JD. Review of AlloDerm acellular human dermis regenerative tissue matrix in multiple types of oculofacial plastic and reconstructive surgery. Ophthalmic Plast Reconstr Surg. 2015;31(5):348e351. 6. Jiaqi C, Zheng W, Jianjun G. Eyelid reconstruction with acellular human dermal allograft after chemical and thermal burns. Burns. 2006;32(2):208e211. 7. Lee EW, Berbos Z, Zaldivar RA, et al. Use of DermaMatrix graft in oculoplastic surgery. Ophthalmic Plast Reconstr Surg. 2010;26(3):153e154.
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8. Li TG, Shorr N, Goldberg RA. Comparison of the efficacy of hard palate grafts with acellular human dermis grafts in lower eyelid surgery. Plast Reconstr Surg. 2005;116(3):873e878. discussion 879e880. 9. Liao SL, Wei YH. Correction of lower lid retraction using TarSys bioengineered grafts for Graves ophthalmopathy. Am J Ophthalmol. 2013;156(2), 387e392 e381. 10. McCord C, Nahai FR, Codner MA, et al. Use of porcine acellular dermal matrix (ENDURAGen) grafts in eyelids: a review of 69 patients and 129 eyelids. Plast Reconstr Surg. 2008;122(4):1206e1213. 11. Scruggs JT, McGwin Jr G, Morgenstern KE. Use of (BellaDerm) in lower eyelid retraction repair. Ophthalmic Plast Reconstr Surg. 2015;31(5):379e384. 12. Shorr N, Perry JD, Goldberg RA, et al. The safety and applications of acellular human dermal allograft in ophthalmic plastic and reconstructive surgery: a preliminary report. Ophthalmic Plast Reconstr Surg. 2000;16(3):223e230.
13. Sullivan SA, Dailey RA. Graft contraction: a comparison of acellular dermis versus hard palate mucosa in lower eyelid surgery. Ophthalmic Plast Reconstr Surg. 2003;19(1): 14e24. 14. Taban M, Douglas R, Li T, et al. Efficacy of “thick” acellular human dermis (AlloDerm) for lower eyelid reconstruction: comparison with hard palate and thin AlloDerm grafts. Arch Facial Plast Surg. 2005;7(1):38e44. 15. Borrelli M, Unterlauft J, Kleinsasser N, Geerling G. Decellularized porcine derived membrane (TarSys(R)) for correction of lower eyelid retraction. Orbit. 2012;31(3):187e189. 16. Kim HJ, Grossniklaus HE, Wojno TH. A cyst-like foreign body reaction to porcine decellularized membrane (TarSys). Ophthalmic Plast Reconstr Surg. 2014;30(4):e100ee102. 17. Grumbine FL, Idowu O, Kersten RC, et al. Correction of lower eyelid retraction with en glove placement of porcine dermal collagen matrix implant. Plast Reconstr Surg. 2019;143(3): 743e746.
Footnotes and Financial Disclosures Originally received: November 14, 2019. Final revision: November 15, 2019. Accepted: November 15, 2019. Available online: ---.
V.K.A.: Consultant e Horizon Therapeutics, Lake Forest, IL (US Operations). Manuscript no. D-19-00734.
1
Gavin Herbert Eye Institute, University of California, Irvine School of Medicine, Irvine, California.
2
Illinois Eye and Ear Infirmary, University of Illinois College of Medicine at Chicago, Chicago, Illinois. 3
Ophthalmic Plastic Surgery, Lions Eye Institute, Department of Ophthalmology, Albany Medical Center, Albany (Slingerlands), New York.
4
Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
5
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
6
Ophthalmic Surgeons and Consultants of Ohio, Columbus, Ohio.
7
Cullen Eye Institute, Baylor College of Medicine, Houston, Texas. Financial Disclosure(s): The author(s) have made the following disclosure(s): J.P.T.: Consultant e Horizon Therapeutics, Lake Forest, IL (US Operations).
E.J.W.: Consultant e Valeant Pharmaceuticals, Bridgewater, NJ; Consultant e Horizon Therapeutics, Lake Forest, IL; Equity Owner e Praxis Biotechnology, Sacramento, CA. S.K.F.: Consultant e Horizon Therapeutics, Lake Forest, IL (US Operations). Funded without commercial support by the American Academy of Ophthalmology. HUMAN SUBJECTS: No human subjects were included in this study. No animal subjects were included in this study. Prepared by the Ophthalmic Technology Assessment Committee Oculoplastics and Orbit Panel and approved by the American Academy of Ophthalmology’s Board of Trustees Month October 11, 2019. Abbreviations and Acronyms: BADM ¼ bioengineered acellular dermal matrix; MRD2 ¼ lower lid margin-to-pupillary reflex distance; TED ¼ thyroid eye disease. Correspondence: Ali Al-Rajhi, PhD, MPH, American Academy of Ophthalmology, Quality and Data Science, P. O. Box 7424, San Francisco, CA 94120-7424. E-mail: [email protected].
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