- Email: [email protected]
Pediatric Anophthalmic Sockets and Orbital Implants
Pediatric Anophthalmic Sockets and Orbital Implants Outcomes with Polymer-Coated Implants Maria Kirzhner, MD,1,2 Yevgeniy Shildkrot, MD,1,2 Barrett G. Haik, MD, FACS,1,2 Ibrahim Qaddoumi, MD,3 Carlos Rodriguez-Galindo, MD,3 Matthew W. Wilson, MD, FACS1,2,4 Purpose: To compare wrapped and polymer-coated hydroxyapatite implants in children undergoing primary enucleation with no adjuvant therapies. Design: Retrospective, interventional cohort study. Participants: All children undergoing primary enucleation without adjuvant therapies between 1999 and 2009 at a tertiary pediatric cancer hospital. Methods: Review and analysis of patient records. Main Outcome Measures: Implant exposure, extrusion and migration, socket contracture, and formation of pyogenic granuloma. Results: Sixty consecutive patients undergoing primary enucleation with no adjuvant chemotherapy or radiation with follow-up of at least 12 months were included. Retinoblastoma was the diagnosis in 59 eyes (98.3%). Median follow-up was 3.6 years (range, 1.0⫺9.3 years). Two implant sizes were used: 20 mm in 47 patients (78.3%) and 18 mm in 13 patients (21.7%). Overall, 52 patients (86.7%) had an event-free recovery. Polymer-coated hydroxyapatite implants (43/60, 71.7%), when compared with wrapped ones (17/60, 28.3%), had a trend toward greater event-free recovery (odds ratio [OR], 1.6; 95% confidence interval [CI], 0.3⫺7.7) and lower exposure rate (OR, 2.1; 95% CI, 0.4⫺10.5). Conclusions: The use of polymer-coated hydroxyapatite implants is associated with favorable outcomes in the pediatric population. Despite observed complications, long-term implant retention is possible in most children. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013;120:1300 –1304 © 2013 by the American Academy of Ophthalmology.
Retinoblastoma is the most common primary intraocular cancer of childhood. In eyes with advanced disease, enucleation is the definitive therapy. Although cancer is a leading reason for pediatric enucleation in some centers, trauma remains an important cause of removal of a pediatric eye. The incidence of complications in pediatric anophthalmic patients is higher than in adults even when no additional therapies are administered.1⫺3 Several implant types have been explored in an attempt to minimize complication rates after enucleation. Hydroxyapatite implants (Integrated Orbital Implants, San Diego, CA) have been used safely and extensively for volume replacement in pediatric sockets after enucleation for retinoblastoma.1,4⫺7 One of the potential advantages of porous implants is fibrovascular ingrowth that may decrease the risk of implant migration over a child’s lifetime.8,9 Surgical manipulation of hydroxyapatite can be hindered by its rough surface, and numerous wrapping materials have been explored to address this problem. The majority of published reports of children with retinoblastoma describe the outcomes using banked sclera.1,5,7 Nonbiological coating ma-
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© 2013 by the American Academy of Ophthalmology Published by Elsevier Inc.
terials, such as polyglactin 910 mesh (Vicryl mesh; Ethicon Inc., Somerville, NJ) and dermal allograft (AlloDerm; LifeCell Corporation, Palo Alto, CA), avoid the potential for transmission of infectious agents that exists with banked sclera. The polymer-coated hydroxyapatite implant (Integrated Orbital Implants) became commercially available in 2003. The proposed advantages of this implant include a smooth coating that allows easier implantation and the ability to attach extraocular muscles directly to the implant. In addition, the coating material differs in its rate of absorption so that rapid absorption posteriorly promotes early fibrovascular ingrowth, whereas slow absorption anteriorly decreases early exposure/extrusion. Although early experience with polymer-coated hydroxyapatite implants has been reported,6 no direct comparison with wrapped hydroxyapatite, particularly in pediatric sockets, has been published. Treatments with radiation or chemotherapy significantly increase the risk of postoperative complications.10 The goal of this study was to compare polymer-coated and wrapped hydroxyapatite implants in patients receiving no adjuvant ISSN 0161-6420/13/$–see front matter http://dx.doi.org/10.1016/j.ophtha.2012.11.022
Kirzhner et al 䡠 Polymer-Coated and Wrapped Pediatric Orbital Implants therapies after enucleation performed over 10 years (1999⫺2009) at a tertiary pediatric cancer hospital.
Materials and Methods This was a single-institution, retrospective, interventional study approved by the institutional review board, with all research adhering to the tenets of the Declaration of Helsinki. A Health Information Portability and Accountability Act⫺compliant patient database was queried for a list of consecutive patients undergoing primary or secondary enucleation between November 1999 and February 2009. Excluded were patients with follow-up of less than 12 months, patients enucleated before arrival at the hospital, patients requiring chemotherapy or external beam radiation therapy (EBRT), and patients receiving no orbital implant. The data extracted from the medical records included sex, race, diagnosis, eye involved, laterality of the disease, age at the time of enucleation, time to enucleation, implant characteristics, history and timing of chemotherapy, and EBRT. The type and timing of various complications and presence of an orbital implant at the last follow-up were recorded. Event-free course was defined as the absence of implant exposure, socket contracture, pyogenic granuloma formation, implant migration, and extrusion. When comparing polymer-coated and traditionally wrapped implants, all wrapping materials were considered as 1 cohort. Descriptive statistics were used to assess the baseline patient and eye characteristics, implant features, and incidence of complications. Quantitative variables were compared using the t test. Chisquare analyses with Pearson coefficients were used to compare the incidence of complications between different implant types. The means of quantitative variables are reported with their standard deviations. Two-tailed P values are reported where appropriate, with P ⬍ 0.05 considered statistically significant. Odds ratios (ORs) are reported with 95% confidence intervals (CIs). Statistical analyses were performed with JMP (version 7.0 for Windows, SAS Institute Inc., Cary NC).
Literature Review Strategy By searching PubMed and Embase, references containing the terms enucleation and implant were selected without any limit on date or language of publication. Citations containing in their title, abstract, or keywords the terms child, pediatric, or retinoblastoma were then reviewed.
Surgical Technique All cases underwent enucleation using a standard approach. Lateral canthotomy was performed in young children when safe removal of an eye would be compromised by a narrow palpebral fissure. A 360-degree conjunctival peritomy was performed around the corneal limbus. The 4 recti muscles were cautiously isolated, placed on a double-locking 5-0 Vicryl suture, and disinserted. Inferior and superior oblique muscles were disinserted from the globe. After gentle outward rotation of the globe, the optic nerve was carefully cut using curved Metzenbaum scissors to obtain a longer section of the nerve. The globe was removed, and fresh tumor tissue was extracted. Hemostasis was maintained with digital pressure while hydroxyapatite orbital implants were prepared. Wrapping materials included polyglactin 910 mesh and dermal allograft. Polyglactin 910 mesh was used to wrap the anterior surface of the implant extending beyond the equator, and the dermal allograft covered only the anterior surface. Both were anchored in a similar fashion using a 4-0 Vicryl suture on a Keith
straight needle. Polymer-coated implants were prepared according to the standard manufacturer’s instructions. Once the implant was inserted into the orbital space, the recti muscles were attached to the anterior surface 3 to 4 mm behind the anticipated anterior pole of the sphere. A 3-layered closure was performed using 5-0 Vicryl sutures on a spatulated needle, closing the deep tenon’s fascia, superficial tenon’s fascia, and conjunctiva. A medium conformer was placed, followed by a temporary tarsorrhaphy. A pressure patch dressing was applied. All patients were seen in follow-up the next day. Patients with retinoblastoma were examined under general anesthesia at increasing intervals, ranging from 3 to 16 weeks, on the basis of the patient’s age, genetic status, and the state of the remaining eye, until the age of 5 years; thereafter, if cooperative, patients were examined in the clinic.
Results During the study interval, 140 eyes of 135 patients were enucleated by 2 surgeons (M.W.W. and B.G.H.) using the technique described earlier. Primary enucleation was performed by a single surgeon (M.W.W.) on 60 eyes of 60 patients who received no antecedent or subsequent chemotherapy, cryotherapy, plaque brachytherapy, or EBRT and who had at least 12 months of follow-up. The majority of these eyes (59, 98.3%) harbored retinoblastoma, and left eyes were more commonly affected (34, 56.7%). The patients included 34 boys (56.7%); 36 (60.0%) were Caucasian, and 18 (30.0%) were African-American. Patients were followed for a median of 3.6 years (range, 1.0⫺9.3 years; mean, 3.9⫾2.1 years) from enucleation. Two implant sizes were used: 20 mm in 47 patients (78.3%) and 18 mm in 13 patients (21.7%). No implants were pegged. Overall, 52 patients (86.7%) had an event-free recovery, with exposure being the most common complication, affecting 7 patients (11.7%). Up to March 25, 2004, wrapped hydroxyapatite implants were used exclusively (17, 28.3%); starting on March 29, 2004, only polymer-coated hydroxyapatite implants were used (43, 71.7%). As is evident in Table 1, there was no significant difference in baseline characteristics, including age at enucleation, time from diagnosis to enucleation, and prevalence of larger (20 mm) implants, between patients receiving wrapped and polymer-coated implants. In addition, the 2 groups were similar in the distribution of race (P ⫽ 0.28), sex (P ⫽ 0.43), prevalence of retinoblastoma (P ⫽ 0.52), and eye involved (P ⫽ 0.43). No patient in either group had a history of diabetes or heart disease. Patients receiving polymer-coated hydroxyapatite implants tended to have an eventfree recovery (OR, 1.6; 95% CI, 0.3⫺7.7) and were less likely to develop exposure (OR, 2.1; 95% CI, 0.4⫺10.5), although this was not statistically significant. A similar proportion (P ⫽ 0.11) of larger, 20-mm spheres were present in both the polymer-coated (36, 83.7%) and wrapped (11, 64.7%) groups. Also, both groups had similar numbers of additional surgeries resulting from exposure and extrusion (P ⫽ 0.89). At the last follow-up, an implant was present in all sockets. Among patients excluded because of follow-up inclusion requirements (⬎12 months of follow-up), no complications developed over the observation period, ranging from 1.7 to 5.6 months. Most of the exposures occurred earlier in the follow-up period at a median of 5.0 months (range, 1.4⫺43.3 months) in both groups (wrapped and polymer coated). Subgroup analysis of the 17 wrapped implants (12 [70.6%] acellular dermis and 5 [29.4%] polyglactin mesh) did not reveal a significant difference in the rate (OR, 1.3; 95% CI, 0.10⫺18.0), timing (P ⫽ 0.70), or resolution of exposure (OR, unable to calculate; P ⫽ 0.38) or in the need for additional surgery (OR, 2.8; 95% CI, 0.1⫺55.2) (Table 2, available at http://aaojournal.org).
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Ophthalmology Volume 120, Number 6, June 2013 Table 1. Baseline Characteristics and Rates of Complications Based on Implant Type
Age at enucleation, yrs* Time from diagnosis to enucleation, days* Follow-up, yrs* 20-mm implants, n (%) Sockets with an implant at last follow-up, n (%) Event-free course, n (%) Exposure, n (%) Maximum exposure size, mm* Time to exposure, mos* Resolved exposure, n (%) Implant extrusion, n (%) Implant migration, n (%) Socket contracture, n (%) Pyogenic granuloma, n (%) Sockets with further eye surgeries, n (%) Additional surgeries per patient*
Polymer-Coated Hydroxyapatite Implants (n ⴝ 43 of 60; 71.7%)
Wrapped Hydroxyapatite Implants (n ⴝ 17 of 60; 28.3%)
2.3 (0.3⫺9.0), 2.6⫾2.0 3.0 (0.0⫺26.0), 4.0⫾4.1
3.0 (1.0⫺5.4), 3.0⫾1.4 5.0 (0.0⫺12.0), 4.0⫾3.0
0.48 0.97
2.8 (1.0⫺5.1), 2.9⫾1.2 36/43 (83.7) 43/43 (100)
5.8 (4.9⫺9.3), 6.4⫾1.6 11/17 (64.7) 17/17 (100)
⬍0.0001 0.11
38/43 (88.4) 4/43 (9.3) 9.0 (1.0⫺11.0), 7.5⫾4.5 6.1 (2.1⫺16.7), 7.7⫾6.3 3/4 (75) 1/43 (2.3) 0/43 (0) 0/43 (0) 0/43 (0) 4/43 (9.3)
14/17 (82.4) 3/17 (17.7) 5.0 (1.0⫺5.0), 3.7⫾2.3 3.7 (1.4⫺43.3), 16.1⫾23.6 2/3 (66.7) 0/17 (0) 0/17 (0) 0/17 (0) 0/17 (0) 2/17 (11.8)
0.54 0.36 0.24 0.51 0.81 0.53
3.5 (1⫺5), 3.3⫾1.7
3.0 (1⫺5), 3.0⫾1.4
0.89
P Value
†
† † †
0.77
*Data reported as median (range), mean ⫾ standard deviation unless otherwise specified. † P value could not be calculated.
Discussion This is the largest study of hydroxyapatite implants used for volume replacement during primary enucleation in a pediatric population reported to date. In these patients receiving no additional therapies, event-free recovery, defined by absence of exposure, socket contracture, implant migration, implant extrusion, and pyogenic granuloma formation, was observed in 87% of cases. Implant exposure of any size was the most common complication, affecting 11.7% of sockets. At the final follow-up, 100% of sockets had an orbital implant in place. The use of orbital implants in children after enucleation improves cosmesis and seems to stimulate the natural growth of orbital structures.4,11,12 Coral-derived hydroxyapatite is a natural, porous material with an open network of channels that permit vascular ingrowth and improve biointegration, which may decrease the risk of migration over a child’s lifetime.8,9,13,14 By using an adult-size 20-mm implant in the majority of the children, implant exchanges have not been necessary as the children grew over the follow-up period. We do not peg implants regardless of age because of the inherent risks.15 Banked sclera,16 polyglactin mesh,17 acellular dermis,18 and retroauricular muscle19 are materials that have been used to wrap porous implants in an attempt to minimize complications.20 However, the wrapping may increase anesthesia time and introduce additional sources of infection. The polymer-coated hydroxyapatite implant was developed to provide the advantage of a bioabsorbable coating without the potential risks of using biological wrapping materials, such as banked sclera. Polylactic-co-glycolic acid and polylactic acid are the polymers used to coat hydroxy-
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apatite. In the polymer-coated implants, polylactic-coglycolic acid coating the posterior surface dissolves at a faster rate, allowing early fibrovascular ingrowth, whereas the polylactic acid coating the anterior surface purportedly remains intact longer, maintaining the attachment of extraocular muscles and protecting the conjunctiva and Tenon’s capsule from the rough anterior face of hydroxyapatite. Available since 2003, these polymer-coated hydroxyapatite implants have been reported to be easy to place with good tissue tolerance and biointegration in a predominantly adult population.6 Our outcomes for anophthalmic orbits receiving no additional therapies may be generalized to the nononcologic pediatric population. A 13% rate of any complication and a 12% exposure rate are consistent with complication rates ranging from 1% to 20% in studies of wrapped hydroxyapatite and a smaller study of polymer-coated hydroxyapatite after enucleation in otherwise untreated pediatric sockets.2,5⫺7 Hydroxyapatite implant placement after enucleation in adults is associated with an exposure rate of 5.1% in pooled data from 1157 patients.21 Exposure rates observed with polyglactin mesh⫺wrapped hydroxyapatite implants are generally lower, ranging from 2.8% to 5.4%.14,15,17 Polyglactin mesh may have an abrasive effect on the overlying Tenon’s capsule and conjunctiva, and the absorption of the mesh may cause inflammatory changes, leading to exposure. Acellular dermis has been described as a wrapping material for porous polyethylene implants.18 However, there is only 1 reported case of its use with hydroxyapatite implants in humans.22 We therefore report the largest group of patients with acellular dermis⫺wrapped hydroxyapatite implants with outcomes similar to those of polyglactin mesh wrap.
Kirzhner et al 䡠 Polymer-Coated and Wrapped Pediatric Orbital Implants No prior studies have compared polymer-coated and wrapped hydroxyapatite implants in matched patient cohorts. When compared with wrapped implants, polymercoated implants seem to have a lower incidence of exposure, although the difference failed to reach statistical significance. A possible explanation for the observed lack of statistical difference in the rates of exposure may be related to the pediatric population having a higher propensity for complications that is not ameliorated by implant characteristics. Alternatively, this study may not have sufficient power to uncover statistically, albeit not clinically, significant superiority of one type of implant over another. No published study has examined untreated pediatric patients as an independent group. By extrapolating from a report looking at adult and pediatric patients together, exposure was seen in approximately 1 of 28 children receiving no additional therapies,6 which is not statistically different from the rate reported in the present study (P ⬎ 0.5). In eyes treated by enucleation alone, polymer-coated hydroxyapatite implants seem to be as safe and effective for volume replacement as the wrapped ones, with a comparable incidence of exposure and no observed socket contracture or implant migration.
Study Limitations Our study was limited by its retrospective design. With a larger number of wrapped implants, the study may have detected a larger difference between cohorts. The strengths of our study included a single-institution design, a predominance of patients with retinoblastoma, representing the most likely pediatric group to require enucleation in developed countries,5,7,23 and a consistency of surgical technique and implant used. In conclusion, in our study of hydroxyapatite implants in untreated pediatric patients, polymer-coated and wrapped hydroxyapatite implants seem to be well tolerated in patients with retinoblastoma. With close follow-up and surgical intervention, implant retention is possible in a majority of the sockets.
References 1. Shields CL, Shields JA, De Potter P, Singh AD. Problems with the hydroxyapatite orbital implant: experience with 250 consecutive cases. Br J Ophthalmol 1994;78:702– 6. 2. Lee V, Subak-Sharpe I, Hungerford JL, et al. Exposure of primary orbital implants in postenucleation retinoblastoma patients. Ophthalmology 2000;107:940 – 6. 3. Li T, Shen J, Duffy MT. Exposure rates of wrapped and unwrapped orbital implants following enucleation. Ophthal Plast Reconstr Surg 2001;17:431–5. 4. Lyle CE, Wilson MW, Li CS, Kaste SC. Comparison of orbital volumes in enucleated patients with unilateral retinoblastoma: hydroxyapatite implants versus silicone implants. Ophthal Plast Reconstr Surg 2007;23:393– 6.
5. Christmas NJ, Van Quill K, Murray TG, et al. Evaluation of efficacy and complications: primary pediatric orbital implants after enucleation. Arch Ophthalmol 2000;118:503– 6. 6. Shields CL, Uysal Y, Marr BP, et al. Experience with the polymer-coated hydroxyapatite implant after enucleation in 126 patients. Ophthalmology 2007;114:367–73. 7. De Potter P, Shields CL, Shields JA, Singh AD. Use of the hydroxyapatite ocular implant in the pediatric population. Arch Ophthalmol 1994;112:208 –12. 8. Shields CL, Shields JA, Eagle RC Jr, De Potter P. Histopathologic evidence of fibrovascular ingrowth four weeks after placement of the hydroxyapatite orbital implant. Am J Ophthalmol 1991;111:363– 6. 9. Bigham WJ, Stanley P, Cahill JM Jr, et al. Fibrovascular ingrowth in porous ocular implants: the effect of material composition, porosity, growth factors, and coatings. Ophthal Plast Reconstr Surg 1999;15:317–25. 10. Shildkrot Y, Kirzhner M, Haik BG, et al. The effect of cancer therapies on pediatric anophthalmic sockets. Ophthalmology 2011;118:2480 – 6. 11. Kaltreider SA, Peake LR, Carter BT. Pediatric enucleation: analysis of volume replacement. Arch Ophthalmol 2001;119: 379 – 84. 12. Fountain TR, Goldberger S, Murphree AL. Orbital development after enucleation in early childhood. Ophthal Plast Reconstr Surg 1999;15:32– 6. 13. Ferrone PJ, Dutton JJ. Rate of vascularization of coralline hydroxyapatite ocular implants. Ophthalmology 1992;99: 376 –9. 14. Yoon JS, Lew H, Kim SJ, Lee SY. Exposure rate of hydroxyapatite orbital implants: a 15-year experience of 802 cases. Ophthalmology 2008;115:566 –72. 15. Jordan DR, Gilberg S, Bawazeer A. Coralline hydroxyapatite orbital implant (Bio-Eye): experience with 158 patients. Ophthal Plast Reconstr Surg 2004;20:69 –74. 16. Custer PL, McCaffery S. Complications of sclera-covered enucleation implants. Ophthalmic Plast Reconstr Surg 2006; 22:269 –73. 17. Jordan DR, Klapper SR, Gilberg SM. The use of vicryl mesh in 200 porous orbital implants: a technique with few exposures. Ophthal Plast Reconstr Surg 2003;19:53– 61. 18. Kadyan A, Sandramouli S. Porous polyethylene (Medpor) orbital implants with primary acellular dermis patch grafts. Orbit 2008;27:19 –23. 19. Naugle TC Jr, Lee AM, Haik BG, Callahan MA. Wrapping hydroxyapatite orbital implants with posterior auricular muscle complex grafts. Am J Ophthalmol 1999;128:495–501. 20. Custer PL, Kennedy RH, Woog JJ, et al. Orbital implants in enucleation surgery: a report by the American Academy of Ophthalmology. Ophthalmology 2003;110:2054 – 61. 21. Custer PL, Trinkaus KM. Porous implant exposure: incidence, management, and morbidity. Ophthal Plast Reconstr Surg 2007;23:1–7. 22. 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. Ophthal Plast Reconstr Surg 2000;16:223–30. 23. Wang JK, Liao SL, Lin LL, et al. Porous orbital implants, wraps, and PEG placement in the pediatric population after enucleation. Am J Ophthalmol 2007;144:109 –16.
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Footnotes and Financial Disclosures Originally received: June 13, 2012. Final revision: November 8, 2012. Accepted: November 13, 2012. Available online: February 8, 2013.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2012-869.
1
Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee.
2
Division of Ophthalmology, Department of Surgery, St. Jude Children’s Research Hospital, Memphis, Tennessee.
3
Division of Solid Tumors, Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee.
4
Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee.
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Grant Support: St. Giles Foundation (New York, NY) and Research to Prevent Blindness, Inc. (New York, NY) (an unrestricted grant to the Department of Ophthalmology). Presented in part at the American Society of Ophthalmic Plastic & Reconstructive Surgery 40th Annual Fall Scientific Symposium, October 21⫺22, 2009, San Francisco, California. Correspondence: Matthew W. Wilson, MD, FACS, Hamilton Eye Institute, 930 Madison Avenue, Room 476, Memphis, TN 38163. E-mail: mwilson5@ uthsc.edu.
Retinoblastoma is the most common primary intraocular cancer of childhood. In eyes with advanced disease, enucleation is the definitive therapy. Although cancer is a leading reason for pediatric enucleation in some centers, trauma remains an important cause of removal of a pediatric eye. The incidence of complications in pediatric anophthalmic patients is higher than in adults even when no additional therapies are administered.1⫺3 Several implant types have been explored in an attempt to minimize complication rates after enucleation. Hydroxyapatite implants (Integrated Orbital Implants, San Diego, CA) have been used safely and extensively for volume replacement in pediatric sockets after enucleation for retinoblastoma.1,4⫺7 One of the potential advantages of porous implants is fibrovascular ingrowth that may decrease the risk of implant migration over a child’s lifetime.8,9 Surgical manipulation of hydroxyapatite can be hindered by its rough surface, and numerous wrapping materials have been explored to address this problem. The majority of published reports of children with retinoblastoma describe the outcomes using banked sclera.1,5,7 Nonbiological coating ma-
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© 2013 by the American Academy of Ophthalmology Published by Elsevier Inc.
terials, such as polyglactin 910 mesh (Vicryl mesh; Ethicon Inc., Somerville, NJ) and dermal allograft (AlloDerm; LifeCell Corporation, Palo Alto, CA), avoid the potential for transmission of infectious agents that exists with banked sclera. The polymer-coated hydroxyapatite implant (Integrated Orbital Implants) became commercially available in 2003. The proposed advantages of this implant include a smooth coating that allows easier implantation and the ability to attach extraocular muscles directly to the implant. In addition, the coating material differs in its rate of absorption so that rapid absorption posteriorly promotes early fibrovascular ingrowth, whereas slow absorption anteriorly decreases early exposure/extrusion. Although early experience with polymer-coated hydroxyapatite implants has been reported,6 no direct comparison with wrapped hydroxyapatite, particularly in pediatric sockets, has been published. Treatments with radiation or chemotherapy significantly increase the risk of postoperative complications.10 The goal of this study was to compare polymer-coated and wrapped hydroxyapatite implants in patients receiving no adjuvant ISSN 0161-6420/13/$–see front matter http://dx.doi.org/10.1016/j.ophtha.2012.11.022
Kirzhner et al 䡠 Polymer-Coated and Wrapped Pediatric Orbital Implants therapies after enucleation performed over 10 years (1999⫺2009) at a tertiary pediatric cancer hospital.
Materials and Methods This was a single-institution, retrospective, interventional study approved by the institutional review board, with all research adhering to the tenets of the Declaration of Helsinki. A Health Information Portability and Accountability Act⫺compliant patient database was queried for a list of consecutive patients undergoing primary or secondary enucleation between November 1999 and February 2009. Excluded were patients with follow-up of less than 12 months, patients enucleated before arrival at the hospital, patients requiring chemotherapy or external beam radiation therapy (EBRT), and patients receiving no orbital implant. The data extracted from the medical records included sex, race, diagnosis, eye involved, laterality of the disease, age at the time of enucleation, time to enucleation, implant characteristics, history and timing of chemotherapy, and EBRT. The type and timing of various complications and presence of an orbital implant at the last follow-up were recorded. Event-free course was defined as the absence of implant exposure, socket contracture, pyogenic granuloma formation, implant migration, and extrusion. When comparing polymer-coated and traditionally wrapped implants, all wrapping materials were considered as 1 cohort. Descriptive statistics were used to assess the baseline patient and eye characteristics, implant features, and incidence of complications. Quantitative variables were compared using the t test. Chisquare analyses with Pearson coefficients were used to compare the incidence of complications between different implant types. The means of quantitative variables are reported with their standard deviations. Two-tailed P values are reported where appropriate, with P ⬍ 0.05 considered statistically significant. Odds ratios (ORs) are reported with 95% confidence intervals (CIs). Statistical analyses were performed with JMP (version 7.0 for Windows, SAS Institute Inc., Cary NC).
Literature Review Strategy By searching PubMed and Embase, references containing the terms enucleation and implant were selected without any limit on date or language of publication. Citations containing in their title, abstract, or keywords the terms child, pediatric, or retinoblastoma were then reviewed.
Surgical Technique All cases underwent enucleation using a standard approach. Lateral canthotomy was performed in young children when safe removal of an eye would be compromised by a narrow palpebral fissure. A 360-degree conjunctival peritomy was performed around the corneal limbus. The 4 recti muscles were cautiously isolated, placed on a double-locking 5-0 Vicryl suture, and disinserted. Inferior and superior oblique muscles were disinserted from the globe. After gentle outward rotation of the globe, the optic nerve was carefully cut using curved Metzenbaum scissors to obtain a longer section of the nerve. The globe was removed, and fresh tumor tissue was extracted. Hemostasis was maintained with digital pressure while hydroxyapatite orbital implants were prepared. Wrapping materials included polyglactin 910 mesh and dermal allograft. Polyglactin 910 mesh was used to wrap the anterior surface of the implant extending beyond the equator, and the dermal allograft covered only the anterior surface. Both were anchored in a similar fashion using a 4-0 Vicryl suture on a Keith
straight needle. Polymer-coated implants were prepared according to the standard manufacturer’s instructions. Once the implant was inserted into the orbital space, the recti muscles were attached to the anterior surface 3 to 4 mm behind the anticipated anterior pole of the sphere. A 3-layered closure was performed using 5-0 Vicryl sutures on a spatulated needle, closing the deep tenon’s fascia, superficial tenon’s fascia, and conjunctiva. A medium conformer was placed, followed by a temporary tarsorrhaphy. A pressure patch dressing was applied. All patients were seen in follow-up the next day. Patients with retinoblastoma were examined under general anesthesia at increasing intervals, ranging from 3 to 16 weeks, on the basis of the patient’s age, genetic status, and the state of the remaining eye, until the age of 5 years; thereafter, if cooperative, patients were examined in the clinic.
Results During the study interval, 140 eyes of 135 patients were enucleated by 2 surgeons (M.W.W. and B.G.H.) using the technique described earlier. Primary enucleation was performed by a single surgeon (M.W.W.) on 60 eyes of 60 patients who received no antecedent or subsequent chemotherapy, cryotherapy, plaque brachytherapy, or EBRT and who had at least 12 months of follow-up. The majority of these eyes (59, 98.3%) harbored retinoblastoma, and left eyes were more commonly affected (34, 56.7%). The patients included 34 boys (56.7%); 36 (60.0%) were Caucasian, and 18 (30.0%) were African-American. Patients were followed for a median of 3.6 years (range, 1.0⫺9.3 years; mean, 3.9⫾2.1 years) from enucleation. Two implant sizes were used: 20 mm in 47 patients (78.3%) and 18 mm in 13 patients (21.7%). No implants were pegged. Overall, 52 patients (86.7%) had an event-free recovery, with exposure being the most common complication, affecting 7 patients (11.7%). Up to March 25, 2004, wrapped hydroxyapatite implants were used exclusively (17, 28.3%); starting on March 29, 2004, only polymer-coated hydroxyapatite implants were used (43, 71.7%). As is evident in Table 1, there was no significant difference in baseline characteristics, including age at enucleation, time from diagnosis to enucleation, and prevalence of larger (20 mm) implants, between patients receiving wrapped and polymer-coated implants. In addition, the 2 groups were similar in the distribution of race (P ⫽ 0.28), sex (P ⫽ 0.43), prevalence of retinoblastoma (P ⫽ 0.52), and eye involved (P ⫽ 0.43). No patient in either group had a history of diabetes or heart disease. Patients receiving polymer-coated hydroxyapatite implants tended to have an eventfree recovery (OR, 1.6; 95% CI, 0.3⫺7.7) and were less likely to develop exposure (OR, 2.1; 95% CI, 0.4⫺10.5), although this was not statistically significant. A similar proportion (P ⫽ 0.11) of larger, 20-mm spheres were present in both the polymer-coated (36, 83.7%) and wrapped (11, 64.7%) groups. Also, both groups had similar numbers of additional surgeries resulting from exposure and extrusion (P ⫽ 0.89). At the last follow-up, an implant was present in all sockets. Among patients excluded because of follow-up inclusion requirements (⬎12 months of follow-up), no complications developed over the observation period, ranging from 1.7 to 5.6 months. Most of the exposures occurred earlier in the follow-up period at a median of 5.0 months (range, 1.4⫺43.3 months) in both groups (wrapped and polymer coated). Subgroup analysis of the 17 wrapped implants (12 [70.6%] acellular dermis and 5 [29.4%] polyglactin mesh) did not reveal a significant difference in the rate (OR, 1.3; 95% CI, 0.10⫺18.0), timing (P ⫽ 0.70), or resolution of exposure (OR, unable to calculate; P ⫽ 0.38) or in the need for additional surgery (OR, 2.8; 95% CI, 0.1⫺55.2) (Table 2, available at http://aaojournal.org).
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Ophthalmology Volume 120, Number 6, June 2013 Table 1. Baseline Characteristics and Rates of Complications Based on Implant Type
Age at enucleation, yrs* Time from diagnosis to enucleation, days* Follow-up, yrs* 20-mm implants, n (%) Sockets with an implant at last follow-up, n (%) Event-free course, n (%) Exposure, n (%) Maximum exposure size, mm* Time to exposure, mos* Resolved exposure, n (%) Implant extrusion, n (%) Implant migration, n (%) Socket contracture, n (%) Pyogenic granuloma, n (%) Sockets with further eye surgeries, n (%) Additional surgeries per patient*
Polymer-Coated Hydroxyapatite Implants (n ⴝ 43 of 60; 71.7%)
Wrapped Hydroxyapatite Implants (n ⴝ 17 of 60; 28.3%)
2.3 (0.3⫺9.0), 2.6⫾2.0 3.0 (0.0⫺26.0), 4.0⫾4.1
3.0 (1.0⫺5.4), 3.0⫾1.4 5.0 (0.0⫺12.0), 4.0⫾3.0
0.48 0.97
2.8 (1.0⫺5.1), 2.9⫾1.2 36/43 (83.7) 43/43 (100)
5.8 (4.9⫺9.3), 6.4⫾1.6 11/17 (64.7) 17/17 (100)
⬍0.0001 0.11
38/43 (88.4) 4/43 (9.3) 9.0 (1.0⫺11.0), 7.5⫾4.5 6.1 (2.1⫺16.7), 7.7⫾6.3 3/4 (75) 1/43 (2.3) 0/43 (0) 0/43 (0) 0/43 (0) 4/43 (9.3)
14/17 (82.4) 3/17 (17.7) 5.0 (1.0⫺5.0), 3.7⫾2.3 3.7 (1.4⫺43.3), 16.1⫾23.6 2/3 (66.7) 0/17 (0) 0/17 (0) 0/17 (0) 0/17 (0) 2/17 (11.8)
0.54 0.36 0.24 0.51 0.81 0.53
3.5 (1⫺5), 3.3⫾1.7
3.0 (1⫺5), 3.0⫾1.4
0.89
P Value
†
† † †
0.77
*Data reported as median (range), mean ⫾ standard deviation unless otherwise specified. † P value could not be calculated.
Discussion This is the largest study of hydroxyapatite implants used for volume replacement during primary enucleation in a pediatric population reported to date. In these patients receiving no additional therapies, event-free recovery, defined by absence of exposure, socket contracture, implant migration, implant extrusion, and pyogenic granuloma formation, was observed in 87% of cases. Implant exposure of any size was the most common complication, affecting 11.7% of sockets. At the final follow-up, 100% of sockets had an orbital implant in place. The use of orbital implants in children after enucleation improves cosmesis and seems to stimulate the natural growth of orbital structures.4,11,12 Coral-derived hydroxyapatite is a natural, porous material with an open network of channels that permit vascular ingrowth and improve biointegration, which may decrease the risk of migration over a child’s lifetime.8,9,13,14 By using an adult-size 20-mm implant in the majority of the children, implant exchanges have not been necessary as the children grew over the follow-up period. We do not peg implants regardless of age because of the inherent risks.15 Banked sclera,16 polyglactin mesh,17 acellular dermis,18 and retroauricular muscle19 are materials that have been used to wrap porous implants in an attempt to minimize complications.20 However, the wrapping may increase anesthesia time and introduce additional sources of infection. The polymer-coated hydroxyapatite implant was developed to provide the advantage of a bioabsorbable coating without the potential risks of using biological wrapping materials, such as banked sclera. Polylactic-co-glycolic acid and polylactic acid are the polymers used to coat hydroxy-
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apatite. In the polymer-coated implants, polylactic-coglycolic acid coating the posterior surface dissolves at a faster rate, allowing early fibrovascular ingrowth, whereas the polylactic acid coating the anterior surface purportedly remains intact longer, maintaining the attachment of extraocular muscles and protecting the conjunctiva and Tenon’s capsule from the rough anterior face of hydroxyapatite. Available since 2003, these polymer-coated hydroxyapatite implants have been reported to be easy to place with good tissue tolerance and biointegration in a predominantly adult population.6 Our outcomes for anophthalmic orbits receiving no additional therapies may be generalized to the nononcologic pediatric population. A 13% rate of any complication and a 12% exposure rate are consistent with complication rates ranging from 1% to 20% in studies of wrapped hydroxyapatite and a smaller study of polymer-coated hydroxyapatite after enucleation in otherwise untreated pediatric sockets.2,5⫺7 Hydroxyapatite implant placement after enucleation in adults is associated with an exposure rate of 5.1% in pooled data from 1157 patients.21 Exposure rates observed with polyglactin mesh⫺wrapped hydroxyapatite implants are generally lower, ranging from 2.8% to 5.4%.14,15,17 Polyglactin mesh may have an abrasive effect on the overlying Tenon’s capsule and conjunctiva, and the absorption of the mesh may cause inflammatory changes, leading to exposure. Acellular dermis has been described as a wrapping material for porous polyethylene implants.18 However, there is only 1 reported case of its use with hydroxyapatite implants in humans.22 We therefore report the largest group of patients with acellular dermis⫺wrapped hydroxyapatite implants with outcomes similar to those of polyglactin mesh wrap.
Kirzhner et al 䡠 Polymer-Coated and Wrapped Pediatric Orbital Implants No prior studies have compared polymer-coated and wrapped hydroxyapatite implants in matched patient cohorts. When compared with wrapped implants, polymercoated implants seem to have a lower incidence of exposure, although the difference failed to reach statistical significance. A possible explanation for the observed lack of statistical difference in the rates of exposure may be related to the pediatric population having a higher propensity for complications that is not ameliorated by implant characteristics. Alternatively, this study may not have sufficient power to uncover statistically, albeit not clinically, significant superiority of one type of implant over another. No published study has examined untreated pediatric patients as an independent group. By extrapolating from a report looking at adult and pediatric patients together, exposure was seen in approximately 1 of 28 children receiving no additional therapies,6 which is not statistically different from the rate reported in the present study (P ⬎ 0.5). In eyes treated by enucleation alone, polymer-coated hydroxyapatite implants seem to be as safe and effective for volume replacement as the wrapped ones, with a comparable incidence of exposure and no observed socket contracture or implant migration.
Study Limitations Our study was limited by its retrospective design. With a larger number of wrapped implants, the study may have detected a larger difference between cohorts. The strengths of our study included a single-institution design, a predominance of patients with retinoblastoma, representing the most likely pediatric group to require enucleation in developed countries,5,7,23 and a consistency of surgical technique and implant used. In conclusion, in our study of hydroxyapatite implants in untreated pediatric patients, polymer-coated and wrapped hydroxyapatite implants seem to be well tolerated in patients with retinoblastoma. With close follow-up and surgical intervention, implant retention is possible in a majority of the sockets.
References 1. Shields CL, Shields JA, De Potter P, Singh AD. Problems with the hydroxyapatite orbital implant: experience with 250 consecutive cases. Br J Ophthalmol 1994;78:702– 6. 2. Lee V, Subak-Sharpe I, Hungerford JL, et al. Exposure of primary orbital implants in postenucleation retinoblastoma patients. Ophthalmology 2000;107:940 – 6. 3. Li T, Shen J, Duffy MT. Exposure rates of wrapped and unwrapped orbital implants following enucleation. Ophthal Plast Reconstr Surg 2001;17:431–5. 4. Lyle CE, Wilson MW, Li CS, Kaste SC. Comparison of orbital volumes in enucleated patients with unilateral retinoblastoma: hydroxyapatite implants versus silicone implants. Ophthal Plast Reconstr Surg 2007;23:393– 6.
5. Christmas NJ, Van Quill K, Murray TG, et al. Evaluation of efficacy and complications: primary pediatric orbital implants after enucleation. Arch Ophthalmol 2000;118:503– 6. 6. Shields CL, Uysal Y, Marr BP, et al. Experience with the polymer-coated hydroxyapatite implant after enucleation in 126 patients. Ophthalmology 2007;114:367–73. 7. De Potter P, Shields CL, Shields JA, Singh AD. Use of the hydroxyapatite ocular implant in the pediatric population. Arch Ophthalmol 1994;112:208 –12. 8. Shields CL, Shields JA, Eagle RC Jr, De Potter P. Histopathologic evidence of fibrovascular ingrowth four weeks after placement of the hydroxyapatite orbital implant. Am J Ophthalmol 1991;111:363– 6. 9. Bigham WJ, Stanley P, Cahill JM Jr, et al. Fibrovascular ingrowth in porous ocular implants: the effect of material composition, porosity, growth factors, and coatings. Ophthal Plast Reconstr Surg 1999;15:317–25. 10. Shildkrot Y, Kirzhner M, Haik BG, et al. The effect of cancer therapies on pediatric anophthalmic sockets. Ophthalmology 2011;118:2480 – 6. 11. Kaltreider SA, Peake LR, Carter BT. Pediatric enucleation: analysis of volume replacement. Arch Ophthalmol 2001;119: 379 – 84. 12. Fountain TR, Goldberger S, Murphree AL. Orbital development after enucleation in early childhood. Ophthal Plast Reconstr Surg 1999;15:32– 6. 13. Ferrone PJ, Dutton JJ. Rate of vascularization of coralline hydroxyapatite ocular implants. Ophthalmology 1992;99: 376 –9. 14. Yoon JS, Lew H, Kim SJ, Lee SY. Exposure rate of hydroxyapatite orbital implants: a 15-year experience of 802 cases. Ophthalmology 2008;115:566 –72. 15. Jordan DR, Gilberg S, Bawazeer A. Coralline hydroxyapatite orbital implant (Bio-Eye): experience with 158 patients. Ophthal Plast Reconstr Surg 2004;20:69 –74. 16. Custer PL, McCaffery S. Complications of sclera-covered enucleation implants. Ophthalmic Plast Reconstr Surg 2006; 22:269 –73. 17. Jordan DR, Klapper SR, Gilberg SM. The use of vicryl mesh in 200 porous orbital implants: a technique with few exposures. Ophthal Plast Reconstr Surg 2003;19:53– 61. 18. Kadyan A, Sandramouli S. Porous polyethylene (Medpor) orbital implants with primary acellular dermis patch grafts. Orbit 2008;27:19 –23. 19. Naugle TC Jr, Lee AM, Haik BG, Callahan MA. Wrapping hydroxyapatite orbital implants with posterior auricular muscle complex grafts. Am J Ophthalmol 1999;128:495–501. 20. Custer PL, Kennedy RH, Woog JJ, et al. Orbital implants in enucleation surgery: a report by the American Academy of Ophthalmology. Ophthalmology 2003;110:2054 – 61. 21. Custer PL, Trinkaus KM. Porous implant exposure: incidence, management, and morbidity. Ophthal Plast Reconstr Surg 2007;23:1–7. 22. 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. Ophthal Plast Reconstr Surg 2000;16:223–30. 23. Wang JK, Liao SL, Lin LL, et al. Porous orbital implants, wraps, and PEG placement in the pediatric population after enucleation. Am J Ophthalmol 2007;144:109 –16.
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Footnotes and Financial Disclosures Originally received: June 13, 2012. Final revision: November 8, 2012. Accepted: November 13, 2012. Available online: February 8, 2013.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2012-869.
1
Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee.
2
Division of Ophthalmology, Department of Surgery, St. Jude Children’s Research Hospital, Memphis, Tennessee.
3
Division of Solid Tumors, Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee.
4
Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee.
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Grant Support: St. Giles Foundation (New York, NY) and Research to Prevent Blindness, Inc. (New York, NY) (an unrestricted grant to the Department of Ophthalmology). Presented in part at the American Society of Ophthalmic Plastic & Reconstructive Surgery 40th Annual Fall Scientific Symposium, October 21⫺22, 2009, San Francisco, California. Correspondence: Matthew W. Wilson, MD, FACS, Hamilton Eye Institute, 930 Madison Avenue, Room 476, Memphis, TN 38163. E-mail: mwilson5@ uthsc.edu.