- Email: [email protected]
Amniotic Membrane Transplantation for Restrictive Strabismus
Amniotic Membrane Transplantation for Restrictive Strabismus Yi Ning J. Strube, MD, FRCSC,1,2 Francisco Conte, MD,1,3 Claudia Faria, MD,1,4 Samuel Yiu, PhD, MD,5 Kenneth W. Wright, MD1,6 Purpose: To report the use of amniotic membrane transplant in patients with restrictive strabismus. Design: Retrospective, interventional case series. Participants: Patients with restrictive strabismus treated with amniotic membrane transplantation. Methods: Chart review of 7 consecutive patients (8 eyes) who developed restrictive strabismus after periocular surgery and were treated with surgical removal of restrictive adhesions and placement of an amniotic membrane transplant. Main Outcome Measures: Intraoperative findings to explain the mechanism of restrictive strabismus, and clinical postoperative results, including ocular alignment, ductions and versions, symptom relief, and resolution of diplopia. Results: Restrictive strabismus occurred after surgery for pterygium, retinal detachment, orbital floor fracture, dermoid cyst, and dermatochalasis. Restrictive strabismus was due to a combination of conjunctival contracture, fat adherence, or rectus muscle contracture. All patients developed postoperative scarring, with failed additional standard surgery to remove the adhesions, including 1 patient treated with mitomycin C for recurrent scarring after pterygium. Reoperation using amniotic membrane transplantation was associated with improvement of ocular motility in 6 of the 7 patients; 1 patient had recurrence of scarring with persistent diplopia. The remaining 6 of 7 patients had no significant recurrence of scarring, and motility remained stable during the follow-up period of 5 to 13 months. Conclusions: Amniotic membrane transplantation seems to help prevent recurrence of adhesions in patients with restrictive strabismus caused by conjunctival scarring, fat adherence syndrome, or rectus muscle contracture. Use of an amniotic membrane transplant should be considered as a treatment option for these difficult cases of restrictive strabismus. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011;118:1175–1179 © 2011 by the American Academy of Ophthalmology.
Restrictive strabismus is an important complication of periocular surgery. Restrictive strabismus has been reported after strabismus surgery,1,2 scleral buckle procedures for retinal detachment,1,3 orbital surgery,4 pterygium surgery,5 and blepharoplasty.6 This form of strabismus is difficult to manage using standard surgical techniques based on simply removing the scar because the adhesions often recur.3,4,7–10 Surgeons have tried various strategies to prevent restrictive adhesions, including the use of synthetic membranes to separate adhesions from the muscle and sclera,8 local injections of corticosteroids,9 and the use of mitomycin C.10 –14 These treatments, however, have not been effective and can even increase scarring induced by the implant material or toxicity from the mitomycin C.14 Tseng et al15 reported the use of amniotic membrane transplantation to successfully reconstruct scarred conjunctival fornix, and Shimazaki et al16 described using amniotic membrane transplantation to treat symblepharon. Amniotic membrane has a thick basement membrane that facilitates migration of epithelial cells, promoting healing with minimal inflammation and fibrosis.15 To our knowledge, there are only © 2011 by the American Academy of Ophthalmology Published by Elsevier Inc.
a few reports in the literature on the use of amniotic membrane transplantation to treat restrictive strabismus. Yamada et al17 published a case report on the successful treatment of restrictive strabismus occurring after retinal detachment surgery, Sheha et al18 described wrapping the extraocular muscles with amniotic membrane in a case of consecutive exotropia, and Kersey and Vivian19 used amniotic membrane in conjunction with mitomycin C in 2 patients with complex strabismus surgery. This article reports a case series describing the use of amniotic membrane transplant to repair restrictive strabismus occurring after a variety of anterior segment, oculoplastic, and retinal surgeries.
Patients and Methods This is a retrospective chart review describing a case series of 7 consecutive patients, seen between August 2007 and April 2010, who underwent amniotic membrane transplantation for restrictive strabismus after previous periocular surgery. Institutional review board approval was obtained from Cedars-Sinai Medical Center, Los Angeles, California. Informed consent was ISSN 0161-6420/11/$–see front matter doi:10.1016/j.ophtha.2010.10.034
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Figure 1. Patient 1, pre-amniotic membrane transplant. Photographs showing horizontal eye movements after lower lid blepharoplasty, before strabismus surgery repair with amniotic membrane transplant. Scarring and contracture in inferior temporal quadrant right eye restricts elevation and adduction and creates a downshoot in adduction. A, Right gaze: normal versions, orthotropia. B, Primary position: exotropia 10 PD and left hypertropia 4 PD. C, Left gaze: right eye shows limited adduction and a downshoot causing a large exotropia and left hypertropia. D, Right eye in attempted elevation and adduction showing the inferior temporal fornix, with scarring and contracture of the conjunctiva. PD ⫽ prism diopters.
acquired from all patients before surgery, and the study was compliant with the Health Insurance Portability and Accountability Act Privacy Rule. The primary surgeon for all surgeries was the senior author (KWW). Blunt and sharp dissection was used to mobilize the conjunctiva and to remove restrictive adhesions along with serial forced ductions to verify improvement of ocular rotations. After scar removal and obtaining full ductions, an amniotic membrane transplant was placed over bare sclera to provide a barrier to prevent recurrent adhesions. If forced ductions were still restricted after mobilizing the conjunctiva and removing scar, the rectus muscles were isolated and if tight, recessed as needed to provide improved ductions intraoperatively, followed by placement of the amniotic membrane transplant. In all 7 cases, human amniotic membrane (Amniograft, Bio-Tissue, Inc., Miami, FL) was transplanted by the method described by Tseng et al15 using fibrin glue (Tisseel Tissue Adhesive Human Fibrin Glue, Baxter AG, Vienna, Austria) to fixate the transplant in place, as previously described.20 To briefly summarize our technique, the amniotic membrane graft was carefully peeled off of the paper in which it is packaged using a pair of non-toothed forceps, each held by the main and assisting surgeons to keep the membrane on stretch. The sticky side of the membrane (the side originally in contact with the
paper) was placed down facing the sclera and positioned to cover the defect as required. Once the membrane was in place as desired, 1 to 2 drops of each tissue glue component was sequentially placed under the membrane and the membrane smoothed over the glue quickly to ensure proper placement, using the non-toothed forceps edge. The glue was allowed to set for several minutes, and any excess dried glue was removed with Westcott scissors. In the most recent case, additional 7-0 Vicryl interrupted sutures were used to secure the edges of the transplant to the cut edge of the conjunctiva in the deep fornices and to the sclera; the sutures were pre-placed before the placement of the tissue glue. The patient’s eye was patched for 24 hours at the end of the case to prevent dislocation of the amniotic membrane transplant.
Results The characteristics, causes of restrictive strabismus, and surgical outcomes of our 7 patients are summarized in Table 1 (available at http://aaojournal.org). Patient 1 is described in detail, because she was the first case to prompt amniotic membrane transplant use and is described as a representative example of our case series.
Figure 2. Patient 1, post-amniotic membrane transplant. Photographs showing almost normal horizontal movements after removal of fat adherence scarring and placement of amniotic membrane transplant in the right inferior temporal quadrant. The only deficit is slight limitation of adduction in left gaze. A, Right gaze: normal versions. B, Primary position: orthotropia. C, Left gaze: Only trace limitation of adduction. D, Right inferior temporal fornix 6 months after amniotic membrane transplant for contracted conjunctiva and fat adherence scarring. There is no significant scarring, and the transplant is not contracted.
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Figure 3. Diagrammatic representation of restrictive strabismus. A, Normal conjunctiva, fornix, and Tenon’s capsule of the inferior orbit. In comparison, restrictive strabismus of the inferior orbit is shown (B), as in patient 1 after lower lid blepharoplasties, with obliterated fornix, conjunctival contracture, and fat adherence scarring from periorbita to sclera.
Case Report: Patient 1 A 76-year-old woman presented with diplopia 4 weeks after bilateral transconjunctival lower-lid blepharoplasty performed by an experienced ophthalmic plastic surgeon. In primary position there was a 10 prism diopter (PD) exotropia and 4 PD left hypertropia. Ductions demonstrated right eye with limited adduction (⫺4) and supraduction (⫺3). Versions showed a significant downshoot of the right eye and large exotropia in left gaze (Fig 1). Surgical exploration of the right eye by the senior author (KWW) revealed positive forced ductions with restriction to supraduction and adduction. There was corresponding conjunctival contracture and fat adherence in the inferior temporal quadrant. Surgical removal of the adhesions and a 7-mm recession of the conjunctiva resolved the restriction. Immediate postoperative examination revealed a surgical success with full ductions and versions and elimination of diplopia. Three weeks after surgery, the restrictive strabismus recurred virtually identical to the strabismus before the author’s repair. A second surgical repair was performed by the same surgeon (KWW), and exploration revealed recurrence of the adhesions in the inferior temporal quadrant and conjunctival contracture. The adhesions were removed again to free forced ductions and the conjunctiva recessed as before, but this time an amniotic membrane transplant was folded into the inferior temporal fornix to cover the exposed sclera. Fibrin tissue glue was used to secure the transplant in place. Postoperatively the ocular motility was much improved, with orthotropia in primary position and only trace limitation of adduction of the right eye (Fig 2). The result was stable with no significant diplopia or recurrence of scarring at 7 months after the amniotic membrane transplant surgery. In our case series, there was a broad range of inciting surgeries causing restrictive strabismus: transconjunctival blepharoplasties in 2 patients (patients 1 and 4), pterygium surgery with mitomycin C in 2 patients (patients 3 and 6), orbital dermoid removal (patient 2), orbital floor fracture repair (patient 5), and retinal detachment surgery with a scleral buckle (patient 7). The mechanism of restrictive strabismus was due to varying degrees and combinations of conjunctival contracture, with significant symblepharon in 3 of the patients (patients 2, 6, and 7), fat adherence in 6 of the patients (patients 1, 2, and 4 –7), and tight rectus muscles in 4 of the patients (patients 2, 3, 6, and 7). Rectus muscle recessions were required in 4 of the 7 patients (patients 2, 3, 6, and 7) because of
persistent restriction despite release of conjunctival contracture and fat adherence scarring. Six of the 7 patients had a successful outcome, based on relief of pain symptoms experienced preoperatively and elimination of diplopia. There were no complications due to the use of the amniotic membrane transplant, and only 1 patient (patient 4) had a dislocation of the amniotic membrane transplant noticed on postoperative day 2. The technique used in our most recent case involved placing 7-0 Vicryl interrupted sutures through the posterior edge of the excised conjunctiva, taking a small bite through sclera and the amniotic membrane transplant. This technique was used to provide more stability to the graft, and to prevent graft dislocation, and is now the technique we use for all such cases. One patient in our case series (patient 4) had recurrence of restrictive strabismus despite amniotic membrane transplant by the senior author (KWW), as well as by her oculoplastic surgeon, with persistent postoperative diplopia at 2 months follow-up, after which she continued follow-up with her oculoplastic surgeon. The range of follow-up for the 6 patients with successful outcome was 5 to 13 months.
Discussion Restriction of ocular motility after periocular surgery is caused by at least 3 mechanisms: (1) conjunctival scarring with contracture; (2) fat adherence to the globe or muscle; and (3) contracture of the rectus muscles (Fig 3). In many cases there is a combination of mechanisms that contribute to the strabismus. Successful treatment of restrictive strabismus requires identifying the specific causes of the restriction. In all of our cases, the restriction was multifactorial. Restrictive strabismus from fat adherence is usually caused by trauma to posterior Tenon’s capsule. Disruption of Tenon’s capsule results in scarring of orbital fat to the globe or extraocular muscles, thus restricting ocular rotations. Restrictive strabismus caused by fat adherence was first described by the late Marshal Parks, which he termed “fat adherence syndrome.” Dr. Parks2 first discovered fat adherence in association with inferior oblique muscle surgery and inadvertent violation of posterior Tenon’s capsule.
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Ophthalmology Volume 118, Number 6, June 2011 Parks emphasized that posterior Tenon’s capsule is an important barrier that separates orbital fat from the globe and extraocular muscles via the muscle sleeve, and violation of that barrier can result in severe restrictive strabismus.3,21 Once orbital fat scars to muscle or sclera, a progressive restriction of ocular rotation occurs as the scar contracts.4 Parks3 emphasized the importance of preventing fat adherence during periocular surgery by using careful surgical dissection, because once fat adherence syndrome occurs it is extremely difficult to impossible to repair. Rectus muscle contracture usually occurs after long-standing conjunctival contracture or fat adherence, resulting in a tight muscle that contributes to the restrictive strabismus. Previous treatments for restrictive strabismus have been relatively unsuccessful. This was demonstrated by the 4 patients who presented to us with previously unsuccessful standard surgery for restrictive strabismus, 3 of whom subsequently had successful outcomes with the use of our amniotic membrane transplant technique. These unsuccessful standard treatments included surgical removal of adhesions alone (patient 1), repeat pterygium excision with mitomycin C and injection with dexamethasone and triamcinolone (patient 3), surgical removal of adhesions and scar removal and use of amniotic membrane transplant by another surgeon (patient 4), and recurrent pterygium excision with mitomycin C alone (patient 6). The use of synthetic membranes to separate adhesions from the muscle and sclera has been tried, but fibrosis envelops the implant, resulting in recurrence of the restriction.8 Local injection of corticosteroids in the area of adhesions has also been used to prevent fibrosis, but it is the authors’ experience that the effect is short-lived and scarring inevitably recurs.9 The effectiveness of mitomycin C and 5-fluorouracil in controlling postoperative adhesions after strabismus surgery has been investigated in the rabbit animal model and in patients with restrictive strabismus with mixed results.11–14 Use of mitomycin C can cause serious complications, including scleral thinning, anterior segment ischemia, and even increased fibrosis.14 Mitomycin C was used in 2 of our patients (patients 3 and 6) to reduce scar before referral, yet the scar and diplopia recurred. We did not use mitomycin C in any of the patients in this series. By using an experimental rabbit animal model of restrictive strabismus, Brooks et al14 showed that mitomycin C applied to the eye to reduce periocular adhesions actually increased periocular scaring and fibrosis. This was thought to be due to the cytotoxicity of mitomycin C causing local tissue necrosis and subsequent fibrosis. Amniotic membrane transplant has been described for the repair of severe conjunctival dehiscence after strabismus surgery22 and to reduce adhesions associated with strabismus surgery.18,19 Amniotic membrane is the innermost avascular layer of the placenta, consisting of a single layer of metabolically active epithelial cells attached to a thick basement membrane and an avascular stromal matrix.23,24 Amniotic membrane is an attractive substrate for use in ophthalmology because it is immunologically inert and provides a substrate for epithelial growth and attachment. Amniotic membrane transplant has the theoretic advantages of reducing inflammation, fibrosis, and angiogenesis, and promoting re-epithelialization of the tissue.25,26 Because of these attributes,
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amniotic membrane transplant has the potential to treat and prevent recurrences of restrictive strabismus. In our series, patients 1, 2, and 4 had fat adherence as a major contributing factor causing the restrictive strabismus. In patients 1 and 2, amniotic membrane transplantation prevented recurrence of restrictive strabismus after previous standard surgery to remove restrictive adhesions failed. Patient 1 is interesting because standard reconstructive surgery performed by one of the authors (KWW) failed to prevent recurrence of conjunctival scarring and fat adherence. Contracted conjunctiva and fat adherence produced severe restriction with limited adduction and a downshoot on attempted adduction (Fig 1). Use of the amniotic membrane transplant addressed both mechanisms. The transplant provided a barrier separating the fat adhesions from reattaching to sclera and a tissue spacer to cover the exposed sclera. The standard surgical approach of removing scar, recessing the conjunctiva, and using topical corticosteroids postoperatively improved forced ductions at the time of surgery, and initial follow-up showed resolution of the restriction. As commonly occurs in these cases, the restrictive strabismus returned a few weeks after surgery virtually identical to before the repair. Subsequent use of the amniotic membrane transplant to separate fat adherence from the sclera and to cover the exposed sclera left by the contracted conjunctiva resulted in resolution of the restriction without recurrence (Fig 2). This case therefore represents a case with an internal control, with both the standard surgery (which failed) and the amniotic membrane transplant surgery (which succeeded) conducted by the same surgeon (KWW). Patients 2, 3, 6, and 7 had tight rectus muscles contributing to the restriction in addition to contracted conjunctiva and periocular adhesions. These were cases of long-standing strabismus, and it is presumed that muscle contracture occurs over time, resulting in a tight rectus muscle. If the rectus muscle is tight by forced ductions, it is important to recess the tight rectus muscle in addition to releasing the restriction from periocular adhesions or contracted conjunctiva. Sequential forced ductions are useful in identifying the cause of the restriction. Repeat forced ductions during the dissection helps identify the tissue causing the restriction. If forced ductions remain restricted after removing the conjunctiva and periocular adhesions, it is likely that the rectus muscle is tight. This can be verified by retropulsing the eye and repeating forced ductions. If the restriction is caused by a tight rectus muscle, the ductions will improve with retropulsion of the eye.27 If the restriction is secondary to contracted conjunctiva or periocular adhesions, the ductions will not improve or worsen with retropulsion. In conclusion, amniotic membrane transplant can be used to replace missing or contracted conjunctiva and reconstruct a tissue barrier that separates orbital fat and adhesions from sclera. Because amniotic membrane has anti-inflammatory and anti-fibrosis characteristics, it may reduce secondary scarring and help prevent recurrence of restrictive strabismus and the diplopia and pain that often accompany this type of strabismus. Amniotic membrane transplant, however, is not a panacea as demonstrated by patient 4. This patient had 2 reconstructive surgeries using amniotic membrane transplant by 2 experienced surgeons, including one
Strube et al 䡠 Amniotic Membrane Transplantation for Restrictive Strabismus of the authors, yet the restrictive strabismus recurred, albeit to a lesser extent. Prevention of conjunctival scarring and fat adherence during the primary surgery remains the best option. To our knowledge, this is the largest case series of amniotic membrane transplants used to treat restrictive strabismus. Our experience has shown that amniotic membrane transplantation may be a useful tool in the treatment of restrictive strabismus.
References 1. Wright KW. Complex strabismus: restriction, paresis, dissociated strabismus, and torticollis. In: Wright KW, Spiegel PH, eds. Pediatric Ophthalmology and Strabismus. 2nd ed. New York: Springer-Verlag; 2003:255– 6. 2. Parks MM. The overacting inferior oblique muscle. The XXXVI Deschweinitz Lecture. Am J Ophthalmol 1974;77:787–97. 3. Parks MM. Causes of the adhesive syndrome. In: Symposium on Strabismus. St. Louis, MO: Mosby; 1978:269 –79. Trans New Orleans Acad Ophthalmol. vol. 26. 4. Wright KW. The fat adherence syndrome and strabismus after retina surgery. Ophthalmology 1986;93:411–5. 5. Ela-Dalman N, Velez FG, Rosenbaum AL. Incomitant esotropia following pterygium excision surgery. Arch Ophthalmol 2007;125:369 –73. 6. Jameson NA, Good WV, Hoyt CS. Fat adherence simulating inferior oblique palsy following blepharoplasty [letter]. Arch Ophthalmol 1992;110:1369. 7. Johnson LV. Adherence syndrome; pseudoparalysis of the lateral or superior rectus muscles. AMA Arch Ophthalmol 1950;44:870 – 8. 8. Dunlap EA. Plastic implants in muscle surgery: a study of the possible use of plastic materials in the management of extraocular motility restrictions. Trans Am Ophthalmol Soc 1967; 65:393– 470. 9. Robinson MR, Lee SS, Rubin BI, et al. Topical corticosteroid therapy for cicatricial conjunctivitis associated with chronic graftversus-host disease. Bone Marrow Transplant 2004;33:1031–5. 10. Cruz OA. Evaluation of mitomycin to limit postoperative adhesions in strabismus surgery. J Pediatr Ophthalmol Strabismus 1996;33:89 –92. 11. Esme A, Yildirim C, Tatlipinar S, et al. Effects of intraoperative sponge mitomycin C and 5-fluorouracil on scar formation following strabismus surgery in rabbits. Strabismus 2004; 12:141– 8.
12. Mora JS, Sprunger DT, Helveston EM, Evan AP. Intraoperative sponge 5-fluorouracil to reduce postoperative scarring in strabismus surgery. J AAPOS 1997;1:92–7. 13. Minguini N, Monteiro de Carvalho KM, Akaishi PM, De Luca IM. Histologic effect of mitomycin C on strabismus surgery in the rabbit. Invest Ophthalmol Vis Sci 2000;41:3399 – 401. 14. Brooks SE, Ribeiro GB, Archer SM, et al. Fat adherence syndrome treated with intraoperative mitomycin-C: a rabbit model. J Pediatr Ophthalmol Strabismus 1996;33:21–7. 15. Tseng SC, Prabhasawat P, Lee SH. Amniotic membrane transplantation for conjunctival surface reconstruction. Am J Ophthalmol 1997;124:765–74. 16. Shimazaki J, Shinozaki N, Tsubota K. Transplantation of amniotic membrane and limbal autograft for patients with recurrent pterygium associated with symblepharon. Br J Ophthalmol 1998;82:235– 40. 17. Yamada M, Shinoda K, Hatakeyama A, et al. Fat adherence syndrome after retinal surgery treated with amniotic membrane transplantation. Am J Ophthalmol 2001;132:280 –2. 18. Sheha H, Casas V, Hayashida Y. The use of amniotic membrane in reducing adhesions after strabismus surgery. J AAPOS 2009;13:99 –101. 19. Kersey JP, Vivian AJ. Mitomycin and amniotic membrane: a new method of reducing adhesions and fibrosis in strabismus surgery. Strabismus 2008;16:116 – 8. 20. Meskin SW, Ritterband DC. Securing conjunctival grafts with fibrin glue. Tech Ophthalmol 2008;6:13–7. 21. Wright KW. Surgical Anatomy. In: Wright KW, Farzavandi S, eds. Color Atlas of Strabismus Surgery: Strategies and Techniques. 3rd ed. New York: Springer; 2007:95. 22. Mocan MC, Azar NF. Amniotic membrane transplantation for the repair of severe conjunctival dehiscence after strabismus surgery with adjustable sutures. Am J Ophthalmol 2005;140:533–4. 23. Rahman I, Said DG, Maharajan VS, Dua HS. Amniotic membrane in ophthalmology: indications and limitations. Eye (Lond) 2009;23:1954 – 61. 24. Dua HS, Gomes JA, King AJ, Maharajan VS. The amniotic membrane in ophthalmology. Surv Ophthalmol 2004;49:51–77. 25. Gomes JA, Romano A, Santos MS, Dua HS. Amniotic membrane use in ophthalmology. Curr Opin Ophthalmol 2005;16:233–40. 26. Tseng SC, Espana EM, Kawakita T, et al. How does amniotic membrane work? Ocul Surf 2004;2:177– 87. 27. Wright KW. Basic Surgical Techniques (Do’s and Don’ts). In: Wright KW, Farzavandi S, eds. Color Atlas of Strabismus Surgery: Strategies and Techniques. 3rd ed. New York: Springer; 2007:114 –5.
Footnotes and Financial Disclosures Originally received: May 10, 2010. Final revision: October 22, 2010. Accepted: October 22, 2010. Available online: February 3, 2011.
6
Keck School of Medicine, Department of Ophthalmology, University of Southern California, Los Angeles, California.
Manuscript no. 2010-654.
1
Wright Foundation for Pediatric Ophthalmology and Strabismus, Los Angeles, California.
2
Department of Ophthalmology, Queen’s University, Kingston, Ontario, Canada.
3
Fundacion Oftalmologica Los Andes, La Serena, Chile.
4
Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
5
Keck School of Medicine, Doheny Eye Center, University of Southern California, Los Angeles, California.
Presented at: the American Academy of Ophthalmology Annual Meeting, Pediatric Ophthalmology and Strabismus Original Papers Session, October 18, 2010, Chicago, Illinois. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Dr. Kenneth W. Wright has patents/royalties with Titan Surgical. Correspondence: Yi Ning J. Strube, MD, FRCSC, Department of Ophthalmology, Queen’s University, Hotel Dieu Hospital, 166 Brock Street, JM6-016, Kingston, Ontario, K7L 5G2, Canada. E-mail: [email protected].
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Restrictive strabismus is an important complication of periocular surgery. Restrictive strabismus has been reported after strabismus surgery,1,2 scleral buckle procedures for retinal detachment,1,3 orbital surgery,4 pterygium surgery,5 and blepharoplasty.6 This form of strabismus is difficult to manage using standard surgical techniques based on simply removing the scar because the adhesions often recur.3,4,7–10 Surgeons have tried various strategies to prevent restrictive adhesions, including the use of synthetic membranes to separate adhesions from the muscle and sclera,8 local injections of corticosteroids,9 and the use of mitomycin C.10 –14 These treatments, however, have not been effective and can even increase scarring induced by the implant material or toxicity from the mitomycin C.14 Tseng et al15 reported the use of amniotic membrane transplantation to successfully reconstruct scarred conjunctival fornix, and Shimazaki et al16 described using amniotic membrane transplantation to treat symblepharon. Amniotic membrane has a thick basement membrane that facilitates migration of epithelial cells, promoting healing with minimal inflammation and fibrosis.15 To our knowledge, there are only © 2011 by the American Academy of Ophthalmology Published by Elsevier Inc.
a few reports in the literature on the use of amniotic membrane transplantation to treat restrictive strabismus. Yamada et al17 published a case report on the successful treatment of restrictive strabismus occurring after retinal detachment surgery, Sheha et al18 described wrapping the extraocular muscles with amniotic membrane in a case of consecutive exotropia, and Kersey and Vivian19 used amniotic membrane in conjunction with mitomycin C in 2 patients with complex strabismus surgery. This article reports a case series describing the use of amniotic membrane transplant to repair restrictive strabismus occurring after a variety of anterior segment, oculoplastic, and retinal surgeries.
Patients and Methods This is a retrospective chart review describing a case series of 7 consecutive patients, seen between August 2007 and April 2010, who underwent amniotic membrane transplantation for restrictive strabismus after previous periocular surgery. Institutional review board approval was obtained from Cedars-Sinai Medical Center, Los Angeles, California. Informed consent was ISSN 0161-6420/11/$–see front matter doi:10.1016/j.ophtha.2010.10.034
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Figure 1. Patient 1, pre-amniotic membrane transplant. Photographs showing horizontal eye movements after lower lid blepharoplasty, before strabismus surgery repair with amniotic membrane transplant. Scarring and contracture in inferior temporal quadrant right eye restricts elevation and adduction and creates a downshoot in adduction. A, Right gaze: normal versions, orthotropia. B, Primary position: exotropia 10 PD and left hypertropia 4 PD. C, Left gaze: right eye shows limited adduction and a downshoot causing a large exotropia and left hypertropia. D, Right eye in attempted elevation and adduction showing the inferior temporal fornix, with scarring and contracture of the conjunctiva. PD ⫽ prism diopters.
acquired from all patients before surgery, and the study was compliant with the Health Insurance Portability and Accountability Act Privacy Rule. The primary surgeon for all surgeries was the senior author (KWW). Blunt and sharp dissection was used to mobilize the conjunctiva and to remove restrictive adhesions along with serial forced ductions to verify improvement of ocular rotations. After scar removal and obtaining full ductions, an amniotic membrane transplant was placed over bare sclera to provide a barrier to prevent recurrent adhesions. If forced ductions were still restricted after mobilizing the conjunctiva and removing scar, the rectus muscles were isolated and if tight, recessed as needed to provide improved ductions intraoperatively, followed by placement of the amniotic membrane transplant. In all 7 cases, human amniotic membrane (Amniograft, Bio-Tissue, Inc., Miami, FL) was transplanted by the method described by Tseng et al15 using fibrin glue (Tisseel Tissue Adhesive Human Fibrin Glue, Baxter AG, Vienna, Austria) to fixate the transplant in place, as previously described.20 To briefly summarize our technique, the amniotic membrane graft was carefully peeled off of the paper in which it is packaged using a pair of non-toothed forceps, each held by the main and assisting surgeons to keep the membrane on stretch. The sticky side of the membrane (the side originally in contact with the
paper) was placed down facing the sclera and positioned to cover the defect as required. Once the membrane was in place as desired, 1 to 2 drops of each tissue glue component was sequentially placed under the membrane and the membrane smoothed over the glue quickly to ensure proper placement, using the non-toothed forceps edge. The glue was allowed to set for several minutes, and any excess dried glue was removed with Westcott scissors. In the most recent case, additional 7-0 Vicryl interrupted sutures were used to secure the edges of the transplant to the cut edge of the conjunctiva in the deep fornices and to the sclera; the sutures were pre-placed before the placement of the tissue glue. The patient’s eye was patched for 24 hours at the end of the case to prevent dislocation of the amniotic membrane transplant.
Results The characteristics, causes of restrictive strabismus, and surgical outcomes of our 7 patients are summarized in Table 1 (available at http://aaojournal.org). Patient 1 is described in detail, because she was the first case to prompt amniotic membrane transplant use and is described as a representative example of our case series.
Figure 2. Patient 1, post-amniotic membrane transplant. Photographs showing almost normal horizontal movements after removal of fat adherence scarring and placement of amniotic membrane transplant in the right inferior temporal quadrant. The only deficit is slight limitation of adduction in left gaze. A, Right gaze: normal versions. B, Primary position: orthotropia. C, Left gaze: Only trace limitation of adduction. D, Right inferior temporal fornix 6 months after amniotic membrane transplant for contracted conjunctiva and fat adherence scarring. There is no significant scarring, and the transplant is not contracted.
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Figure 3. Diagrammatic representation of restrictive strabismus. A, Normal conjunctiva, fornix, and Tenon’s capsule of the inferior orbit. In comparison, restrictive strabismus of the inferior orbit is shown (B), as in patient 1 after lower lid blepharoplasties, with obliterated fornix, conjunctival contracture, and fat adherence scarring from periorbita to sclera.
Case Report: Patient 1 A 76-year-old woman presented with diplopia 4 weeks after bilateral transconjunctival lower-lid blepharoplasty performed by an experienced ophthalmic plastic surgeon. In primary position there was a 10 prism diopter (PD) exotropia and 4 PD left hypertropia. Ductions demonstrated right eye with limited adduction (⫺4) and supraduction (⫺3). Versions showed a significant downshoot of the right eye and large exotropia in left gaze (Fig 1). Surgical exploration of the right eye by the senior author (KWW) revealed positive forced ductions with restriction to supraduction and adduction. There was corresponding conjunctival contracture and fat adherence in the inferior temporal quadrant. Surgical removal of the adhesions and a 7-mm recession of the conjunctiva resolved the restriction. Immediate postoperative examination revealed a surgical success with full ductions and versions and elimination of diplopia. Three weeks after surgery, the restrictive strabismus recurred virtually identical to the strabismus before the author’s repair. A second surgical repair was performed by the same surgeon (KWW), and exploration revealed recurrence of the adhesions in the inferior temporal quadrant and conjunctival contracture. The adhesions were removed again to free forced ductions and the conjunctiva recessed as before, but this time an amniotic membrane transplant was folded into the inferior temporal fornix to cover the exposed sclera. Fibrin tissue glue was used to secure the transplant in place. Postoperatively the ocular motility was much improved, with orthotropia in primary position and only trace limitation of adduction of the right eye (Fig 2). The result was stable with no significant diplopia or recurrence of scarring at 7 months after the amniotic membrane transplant surgery. In our case series, there was a broad range of inciting surgeries causing restrictive strabismus: transconjunctival blepharoplasties in 2 patients (patients 1 and 4), pterygium surgery with mitomycin C in 2 patients (patients 3 and 6), orbital dermoid removal (patient 2), orbital floor fracture repair (patient 5), and retinal detachment surgery with a scleral buckle (patient 7). The mechanism of restrictive strabismus was due to varying degrees and combinations of conjunctival contracture, with significant symblepharon in 3 of the patients (patients 2, 6, and 7), fat adherence in 6 of the patients (patients 1, 2, and 4 –7), and tight rectus muscles in 4 of the patients (patients 2, 3, 6, and 7). Rectus muscle recessions were required in 4 of the 7 patients (patients 2, 3, 6, and 7) because of
persistent restriction despite release of conjunctival contracture and fat adherence scarring. Six of the 7 patients had a successful outcome, based on relief of pain symptoms experienced preoperatively and elimination of diplopia. There were no complications due to the use of the amniotic membrane transplant, and only 1 patient (patient 4) had a dislocation of the amniotic membrane transplant noticed on postoperative day 2. The technique used in our most recent case involved placing 7-0 Vicryl interrupted sutures through the posterior edge of the excised conjunctiva, taking a small bite through sclera and the amniotic membrane transplant. This technique was used to provide more stability to the graft, and to prevent graft dislocation, and is now the technique we use for all such cases. One patient in our case series (patient 4) had recurrence of restrictive strabismus despite amniotic membrane transplant by the senior author (KWW), as well as by her oculoplastic surgeon, with persistent postoperative diplopia at 2 months follow-up, after which she continued follow-up with her oculoplastic surgeon. The range of follow-up for the 6 patients with successful outcome was 5 to 13 months.
Discussion Restriction of ocular motility after periocular surgery is caused by at least 3 mechanisms: (1) conjunctival scarring with contracture; (2) fat adherence to the globe or muscle; and (3) contracture of the rectus muscles (Fig 3). In many cases there is a combination of mechanisms that contribute to the strabismus. Successful treatment of restrictive strabismus requires identifying the specific causes of the restriction. In all of our cases, the restriction was multifactorial. Restrictive strabismus from fat adherence is usually caused by trauma to posterior Tenon’s capsule. Disruption of Tenon’s capsule results in scarring of orbital fat to the globe or extraocular muscles, thus restricting ocular rotations. Restrictive strabismus caused by fat adherence was first described by the late Marshal Parks, which he termed “fat adherence syndrome.” Dr. Parks2 first discovered fat adherence in association with inferior oblique muscle surgery and inadvertent violation of posterior Tenon’s capsule.
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Ophthalmology Volume 118, Number 6, June 2011 Parks emphasized that posterior Tenon’s capsule is an important barrier that separates orbital fat from the globe and extraocular muscles via the muscle sleeve, and violation of that barrier can result in severe restrictive strabismus.3,21 Once orbital fat scars to muscle or sclera, a progressive restriction of ocular rotation occurs as the scar contracts.4 Parks3 emphasized the importance of preventing fat adherence during periocular surgery by using careful surgical dissection, because once fat adherence syndrome occurs it is extremely difficult to impossible to repair. Rectus muscle contracture usually occurs after long-standing conjunctival contracture or fat adherence, resulting in a tight muscle that contributes to the restrictive strabismus. Previous treatments for restrictive strabismus have been relatively unsuccessful. This was demonstrated by the 4 patients who presented to us with previously unsuccessful standard surgery for restrictive strabismus, 3 of whom subsequently had successful outcomes with the use of our amniotic membrane transplant technique. These unsuccessful standard treatments included surgical removal of adhesions alone (patient 1), repeat pterygium excision with mitomycin C and injection with dexamethasone and triamcinolone (patient 3), surgical removal of adhesions and scar removal and use of amniotic membrane transplant by another surgeon (patient 4), and recurrent pterygium excision with mitomycin C alone (patient 6). The use of synthetic membranes to separate adhesions from the muscle and sclera has been tried, but fibrosis envelops the implant, resulting in recurrence of the restriction.8 Local injection of corticosteroids in the area of adhesions has also been used to prevent fibrosis, but it is the authors’ experience that the effect is short-lived and scarring inevitably recurs.9 The effectiveness of mitomycin C and 5-fluorouracil in controlling postoperative adhesions after strabismus surgery has been investigated in the rabbit animal model and in patients with restrictive strabismus with mixed results.11–14 Use of mitomycin C can cause serious complications, including scleral thinning, anterior segment ischemia, and even increased fibrosis.14 Mitomycin C was used in 2 of our patients (patients 3 and 6) to reduce scar before referral, yet the scar and diplopia recurred. We did not use mitomycin C in any of the patients in this series. By using an experimental rabbit animal model of restrictive strabismus, Brooks et al14 showed that mitomycin C applied to the eye to reduce periocular adhesions actually increased periocular scaring and fibrosis. This was thought to be due to the cytotoxicity of mitomycin C causing local tissue necrosis and subsequent fibrosis. Amniotic membrane transplant has been described for the repair of severe conjunctival dehiscence after strabismus surgery22 and to reduce adhesions associated with strabismus surgery.18,19 Amniotic membrane is the innermost avascular layer of the placenta, consisting of a single layer of metabolically active epithelial cells attached to a thick basement membrane and an avascular stromal matrix.23,24 Amniotic membrane is an attractive substrate for use in ophthalmology because it is immunologically inert and provides a substrate for epithelial growth and attachment. Amniotic membrane transplant has the theoretic advantages of reducing inflammation, fibrosis, and angiogenesis, and promoting re-epithelialization of the tissue.25,26 Because of these attributes,
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amniotic membrane transplant has the potential to treat and prevent recurrences of restrictive strabismus. In our series, patients 1, 2, and 4 had fat adherence as a major contributing factor causing the restrictive strabismus. In patients 1 and 2, amniotic membrane transplantation prevented recurrence of restrictive strabismus after previous standard surgery to remove restrictive adhesions failed. Patient 1 is interesting because standard reconstructive surgery performed by one of the authors (KWW) failed to prevent recurrence of conjunctival scarring and fat adherence. Contracted conjunctiva and fat adherence produced severe restriction with limited adduction and a downshoot on attempted adduction (Fig 1). Use of the amniotic membrane transplant addressed both mechanisms. The transplant provided a barrier separating the fat adhesions from reattaching to sclera and a tissue spacer to cover the exposed sclera. The standard surgical approach of removing scar, recessing the conjunctiva, and using topical corticosteroids postoperatively improved forced ductions at the time of surgery, and initial follow-up showed resolution of the restriction. As commonly occurs in these cases, the restrictive strabismus returned a few weeks after surgery virtually identical to before the repair. Subsequent use of the amniotic membrane transplant to separate fat adherence from the sclera and to cover the exposed sclera left by the contracted conjunctiva resulted in resolution of the restriction without recurrence (Fig 2). This case therefore represents a case with an internal control, with both the standard surgery (which failed) and the amniotic membrane transplant surgery (which succeeded) conducted by the same surgeon (KWW). Patients 2, 3, 6, and 7 had tight rectus muscles contributing to the restriction in addition to contracted conjunctiva and periocular adhesions. These were cases of long-standing strabismus, and it is presumed that muscle contracture occurs over time, resulting in a tight rectus muscle. If the rectus muscle is tight by forced ductions, it is important to recess the tight rectus muscle in addition to releasing the restriction from periocular adhesions or contracted conjunctiva. Sequential forced ductions are useful in identifying the cause of the restriction. Repeat forced ductions during the dissection helps identify the tissue causing the restriction. If forced ductions remain restricted after removing the conjunctiva and periocular adhesions, it is likely that the rectus muscle is tight. This can be verified by retropulsing the eye and repeating forced ductions. If the restriction is caused by a tight rectus muscle, the ductions will improve with retropulsion of the eye.27 If the restriction is secondary to contracted conjunctiva or periocular adhesions, the ductions will not improve or worsen with retropulsion. In conclusion, amniotic membrane transplant can be used to replace missing or contracted conjunctiva and reconstruct a tissue barrier that separates orbital fat and adhesions from sclera. Because amniotic membrane has anti-inflammatory and anti-fibrosis characteristics, it may reduce secondary scarring and help prevent recurrence of restrictive strabismus and the diplopia and pain that often accompany this type of strabismus. Amniotic membrane transplant, however, is not a panacea as demonstrated by patient 4. This patient had 2 reconstructive surgeries using amniotic membrane transplant by 2 experienced surgeons, including one
Strube et al 䡠 Amniotic Membrane Transplantation for Restrictive Strabismus of the authors, yet the restrictive strabismus recurred, albeit to a lesser extent. Prevention of conjunctival scarring and fat adherence during the primary surgery remains the best option. To our knowledge, this is the largest case series of amniotic membrane transplants used to treat restrictive strabismus. Our experience has shown that amniotic membrane transplantation may be a useful tool in the treatment of restrictive strabismus.
References 1. Wright KW. Complex strabismus: restriction, paresis, dissociated strabismus, and torticollis. In: Wright KW, Spiegel PH, eds. Pediatric Ophthalmology and Strabismus. 2nd ed. New York: Springer-Verlag; 2003:255– 6. 2. Parks MM. The overacting inferior oblique muscle. The XXXVI Deschweinitz Lecture. Am J Ophthalmol 1974;77:787–97. 3. Parks MM. Causes of the adhesive syndrome. In: Symposium on Strabismus. St. Louis, MO: Mosby; 1978:269 –79. Trans New Orleans Acad Ophthalmol. vol. 26. 4. Wright KW. The fat adherence syndrome and strabismus after retina surgery. Ophthalmology 1986;93:411–5. 5. Ela-Dalman N, Velez FG, Rosenbaum AL. Incomitant esotropia following pterygium excision surgery. Arch Ophthalmol 2007;125:369 –73. 6. Jameson NA, Good WV, Hoyt CS. Fat adherence simulating inferior oblique palsy following blepharoplasty [letter]. Arch Ophthalmol 1992;110:1369. 7. Johnson LV. Adherence syndrome; pseudoparalysis of the lateral or superior rectus muscles. AMA Arch Ophthalmol 1950;44:870 – 8. 8. Dunlap EA. Plastic implants in muscle surgery: a study of the possible use of plastic materials in the management of extraocular motility restrictions. Trans Am Ophthalmol Soc 1967; 65:393– 470. 9. Robinson MR, Lee SS, Rubin BI, et al. Topical corticosteroid therapy for cicatricial conjunctivitis associated with chronic graftversus-host disease. Bone Marrow Transplant 2004;33:1031–5. 10. Cruz OA. Evaluation of mitomycin to limit postoperative adhesions in strabismus surgery. J Pediatr Ophthalmol Strabismus 1996;33:89 –92. 11. Esme A, Yildirim C, Tatlipinar S, et al. Effects of intraoperative sponge mitomycin C and 5-fluorouracil on scar formation following strabismus surgery in rabbits. Strabismus 2004; 12:141– 8.
12. Mora JS, Sprunger DT, Helveston EM, Evan AP. Intraoperative sponge 5-fluorouracil to reduce postoperative scarring in strabismus surgery. J AAPOS 1997;1:92–7. 13. Minguini N, Monteiro de Carvalho KM, Akaishi PM, De Luca IM. Histologic effect of mitomycin C on strabismus surgery in the rabbit. Invest Ophthalmol Vis Sci 2000;41:3399 – 401. 14. Brooks SE, Ribeiro GB, Archer SM, et al. Fat adherence syndrome treated with intraoperative mitomycin-C: a rabbit model. J Pediatr Ophthalmol Strabismus 1996;33:21–7. 15. Tseng SC, Prabhasawat P, Lee SH. Amniotic membrane transplantation for conjunctival surface reconstruction. Am J Ophthalmol 1997;124:765–74. 16. Shimazaki J, Shinozaki N, Tsubota K. Transplantation of amniotic membrane and limbal autograft for patients with recurrent pterygium associated with symblepharon. Br J Ophthalmol 1998;82:235– 40. 17. Yamada M, Shinoda K, Hatakeyama A, et al. Fat adherence syndrome after retinal surgery treated with amniotic membrane transplantation. Am J Ophthalmol 2001;132:280 –2. 18. Sheha H, Casas V, Hayashida Y. The use of amniotic membrane in reducing adhesions after strabismus surgery. J AAPOS 2009;13:99 –101. 19. Kersey JP, Vivian AJ. Mitomycin and amniotic membrane: a new method of reducing adhesions and fibrosis in strabismus surgery. Strabismus 2008;16:116 – 8. 20. Meskin SW, Ritterband DC. Securing conjunctival grafts with fibrin glue. Tech Ophthalmol 2008;6:13–7. 21. Wright KW. Surgical Anatomy. In: Wright KW, Farzavandi S, eds. Color Atlas of Strabismus Surgery: Strategies and Techniques. 3rd ed. New York: Springer; 2007:95. 22. Mocan MC, Azar NF. Amniotic membrane transplantation for the repair of severe conjunctival dehiscence after strabismus surgery with adjustable sutures. Am J Ophthalmol 2005;140:533–4. 23. Rahman I, Said DG, Maharajan VS, Dua HS. Amniotic membrane in ophthalmology: indications and limitations. Eye (Lond) 2009;23:1954 – 61. 24. Dua HS, Gomes JA, King AJ, Maharajan VS. The amniotic membrane in ophthalmology. Surv Ophthalmol 2004;49:51–77. 25. Gomes JA, Romano A, Santos MS, Dua HS. Amniotic membrane use in ophthalmology. Curr Opin Ophthalmol 2005;16:233–40. 26. Tseng SC, Espana EM, Kawakita T, et al. How does amniotic membrane work? Ocul Surf 2004;2:177– 87. 27. Wright KW. Basic Surgical Techniques (Do’s and Don’ts). In: Wright KW, Farzavandi S, eds. Color Atlas of Strabismus Surgery: Strategies and Techniques. 3rd ed. New York: Springer; 2007:114 –5.
Footnotes and Financial Disclosures Originally received: May 10, 2010. Final revision: October 22, 2010. Accepted: October 22, 2010. Available online: February 3, 2011.
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Keck School of Medicine, Department of Ophthalmology, University of Southern California, Los Angeles, California.
Manuscript no. 2010-654.
1
Wright Foundation for Pediatric Ophthalmology and Strabismus, Los Angeles, California.
2
Department of Ophthalmology, Queen’s University, Kingston, Ontario, Canada.
3
Fundacion Oftalmologica Los Andes, La Serena, Chile.
4
Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
5
Keck School of Medicine, Doheny Eye Center, University of Southern California, Los Angeles, California.
Presented at: the American Academy of Ophthalmology Annual Meeting, Pediatric Ophthalmology and Strabismus Original Papers Session, October 18, 2010, Chicago, Illinois. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Dr. Kenneth W. Wright has patents/royalties with Titan Surgical. Correspondence: Yi Ning J. Strube, MD, FRCSC, Department of Ophthalmology, Queen’s University, Hotel Dieu Hospital, 166 Brock Street, JM6-016, Kingston, Ontario, K7L 5G2, Canada. E-mail: [email protected].
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