Graefe’s Arch Clin Exp Ophthalmol (2006) 244: 232–236
SH ORT COMMUNI CATIO N
DOI 10.1007/s00417-005-0010-y
Yu-Feng Yao Wen-Ya Qiu Yong-Ming Zhang Scheffer C. G. Tseng
Received: 12 January 2005 Revised: 18 February 2005 Accepted: 10 April 2005 Published online: 12 July 2005 # Springer-Verlag 2005
S.C.G.T. and his family are more than 5% shareholders of TissueTech, Inc., which owns US Patents nos 6,152,142 and 6,326,019 on the method of preparation and clinical uses of human amniotic membrane. Y.-F. Yao (*) . W.-Y. Qiu . Y.-M. Zhang Department of Ophthalmology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 Qinchun Road East, Hangzhou, 310016 Zhejiang, People’s Republic of China e-mail:
[email protected] Tel.: +86-571-86090073 Fax: +86-571-86044817 S. C. G. Tseng Ocular Surface Center, Miami, FL, USA
Mitomycin C, amniotic membrane transplantation and limbal conjunctival autograft for treating multirecurrent pterygia with symblepharon and motility restriction
Abstract Background: Treatment of eyes with multirecurrent pterygia associated with severe symblepharon and motility restriction is challenging. A combined surgical procedure of intraoperative mitomycin C, amniotic membrane transplantation and conjunctival limbal autograft was applied for treating such eyes. Methods: Seven eyes of seven patients who had previously undergone an average of four operations for pterygial removal and who manifested recurrent pterygia associated with severe symblepharon and motility restriction were involved in this retrospective study. The surgical procedures involved clearing fibrovascular membrane over the cornea, extensive excision of epibulbar fibrovascular tissue to the bare sclera, application of 0.02% mytomycin C onto the bare sclera for 5 min and transplantation of preserved human amniotic membrane and conjunctival limbal autograft. Results: Postoperatively, all seven
Introduction Pterygium is a common ocular surface disease characterized by overgrowth of conjunctival fibrovascular tissue onto the cornea. Although a number of surgical procedures have been attempted, relentless recurrence remains a great challenge. No single procedure can achieve a satisfactory result in eyes with aggressive recurrence [4]. Repeated surgical failures may result in symblepharon, ocular motility restriction and corneal scarring [4]. Following pterygial excision, covering the bared sclera with a conjunctival au-
eyes showed rapid epithelialization on the corneal surface in 3–5 days and, on the conjunctival surface, in 10–18 days. For a mean follow-up period of 22.4±6.1 months, six eyes recovered deep fornices, smooth and stable ocular surface and full ocular motility without recurrence. One eye showed regrowth of fibrovascular tissue and motility restriction but less severe than before surgery. No complication was noted due to mitomycin C. Conclusions: Combined intraoperative mitomycin C, amniotic membrane graft and limbal conjunctival autograft are successful approaches for treating multirecurrent pterygia with severe symblepharon to restore the ocular surface integrity and prevent recurrence. Keywords Mitomycin C . Symblepharon . Amniotic membrane transplantation . Recurrent pterygia . Limbal conjunctival autograft . Motility restriction
tograft (CAU) [5] or treating it with mitomycin C (MMC) [2, 6] is effective in reducing recurrence. As an alternative to CAU, amniotic membrane transplantation alone (AMT) [7], AMT with CAU [10] or AMT with conjunctival limbal autograft (CLAU) [11] has also been proposed. Nevertheless, in treating recurrent pterygia, the recurrence rates were still as high as 14.3–66.7% in using MMC alone [2, 6], 33.3% in using AMT alone [7], 53% in using AMT with CAU [10] and 25% in using AMT with CLAU [11], respectively.
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For complicated cases, especially in the eyes with multirecurrent pterygia manifesting severe symblepharon and motility restriction, it appears to be agreed that no single and simple method can achieve satisfactory results [4]. Recently, a combined approach has successfully been tested in treating multirecurrent pterygia in a report of two cases [9]. We reported herein our encouraging results in treating seven eyes with multirecurrent pterygia manifesting severe symblepharon and motility restriction through a multidisciplinary reconstructional approach. Our surgical strategy is designed to achieve a simultaneous effect through intraoperative MMC to inhibit subconjunctival fibrovascular proliferation, AMT to provide substrate to cover the large defected area after excision and CLAU to reconstruct the limbal barrier function and create a new conjunctival surface after epithelialization on the AM.
Patients and methods Conforming to the tenets of the Declaration of Helsinki regarding to research involving human subjects, this retrospective study was approved by the Ethics Committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Informed consent was obtained from all pa-
Fig. 1 Preoperative and postoperative appearance of case 1 (top panel), case 4 (middle panel) and case 3 (bottom panel). Preoperative appearances (left panel) showing severe symblepharon of the eyelids and the nasal caruncle adherence to the cornea and severe restriction of ocular motility, in which the eyes had undergone five (a), four (c) and four (e) operations for pterygial removal, respectively. Postoperative appearance (right panel) showing deep fornix without recurrence 32 (b) and 25 months (d) after surgery in case 1 and case 4. Postoperative appearance (right panel, f) of case 3 showing regrowth of fibrovascular tissue in the nasal caruncle to the limbus 9 months after surgery
tients. The inclusion criteria were eyes with multirecurrent pterygia manifesting symblepharon, motility restriction and diplopia at the primary gaze. They all had a minimum of 12 months of postoperative follow-up. Seven eyes of seven patients met the inclusion criteria. Three representative eyes before surgery are shown in Fig. 1. Patients Surgery involving the triple procedures of MMC, AMT and CLAU was consecutively performed by the same surgeon (Y.F.Y.) for all the seven eyes during the period from February 1998 to January 2002. Demographic data are summarized in Table 1. The ages of the patients ranged from 41 to 64 years old (52.1±8.1 years, mean±SD). In all the seven eyes, the recurrent pterygia in the nasal region involved part or whole pupil area of the cornea (in three of seven eyes, the pupil area was completely covered by fibrovascular membrane), which caused severe symblepharon and severe restriction of ocular motility especially in the horizontal direction. The past ocular history of the patients revealed that the period from the first surgery to their referral to us ranged from 3 to 17 years (9.3±5.4 years). During this period, one eye had received five, four eyes had
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Table 1 Clinical data. Pre-VA Corrected visual acuity before surgery, Post-VA corrected visual acuity after surgery Case no.
Age/sex
1 2 3 4 5 6 7
History from first surgical removal (year)
57/F 41/M 53/F 54/F 46/F 64/M 62/F
17 3 7 6 5 15 12
Previous operations
5 3 4 4 3 4 4
Case no.
Severe ocular motility restriction, preoperatively
Postoperative ocular motility
1 2 3 4 5 6 7
Yes Yes Yes Yes Yes Yes Yes
Full recovery in all directions Full recovery in all directions Partial horizontal restriction Full recovery in all directions Full recovery in all directions Full recovery in all directions Full recovery in all directions
Case no.
Pre-VA
Post-VA
Recurrence
Follow-up (months)
1 2 3
0.2 0.1 0.25
0.6 0.6 0.4
32 18 21
4 5 6 7
FC 0.8 0.02 0.15
0.06 1.2 0.05 0.25
no no yes, but less severe no no no no
fornices and the nasal caruncle in all eyes except for case 3, who presented a relatively normal nasal caruncle (Fig. 1e). A piece of cotton ball soaked in 0.02% MMC was applied for 5 min onto the bare sclera involving the exposed rectus muscle and the nasal caruncle and underneath the surrounding conjunctival epithelial margins. Thereafter, the bare scleral surface was irrigated with 40 ml of balanced salt solution. AM was prepared as previously described [10, 11] and was preserved at −20°C. After thawing, the preserved AM was overlaid onto the exposed scleral and corneal surfaces and was inserted underneath the conjunctival edges. The AM was sutured to the denuded cornea by a 10–0 nylon running suture around the limbus and the corneal wound margin and to the bared sclera by 10–0 nylon interrupted sutures. The surrounding conjunctival edges were secured onto the amniotic membrane by 10–0 nylon interrupted sutures with episcleral bites. CLAU in the size of 4×6 mm was obtained from the contralateral eye as previously described [15] and was transferred to cover the corresponding area over AM and secured by episcleral bites of 10–0 nylon interrupted sutures around the limbus. The representative surgical procedures (for case 2) are shown in Fig. 2. At the end of the surgery, 0.1% dexamethasone and 0.3% tobramycin ointment (Alcon Laboratories, Fort Worth, Tex., USA) was applied. Postoperative care and follow-up
received four and two eyes had received three surgical procedures for removal (average of four times per eye). Unfortunately, the past surgical procedure was not exactly clear because they had been performed in other hospitals.
Routinely, the operated eyes received 0.1% dexamethasone and 0.3% tobramycin eye drops (Alcon Laboratories) 4 times daily for 1 month and then shifted to 0.1% fluoromethrone eye drops (Santen Pharmaceutical Co, Osaka, Japan) 4 times daily and 0.3% ofloxacin eye drops (Santen Pharmaceutical Co) 3 times daily thereafter and tapered off in 3 months. All patients were observed daily for the first week, twice weekly for the first month, monthly for the first 3 months, every 2 months for the remaining year and different intervals thereafter. The interrupted sutures on CLAU and AM were removed in 14 days. The running suture was not removed for the first three cases but was removed in 14–18 days for the remaining four cases.
Surgical techniques
Results
After retrobulbar anesthesia, 2% lidocaine was injected into the subconjunctival space to elevate the epithelial layer from the underlying fibrovascular tissue at the head and body region. A small incision of the epithelial layer was made by scissors, followed by insertion of the scissor tips to separate the head from the underlying tissue. The corneal surface was scraped off the remaining fibrovascular tissue until it was smooth. The subconjunctival fibrovascular tissue was thoroughly removed from the sclera by scissors to include the area from the limbus to the superior and inferior
Postoperatively, for all seven eyes, epithelialization migrated from the margin of CLAU onto the AM-covered corneal surface on day 1 and was complete in 3–5 days. Epithelialization on the AM-covered bared sclera originated from the margin of the CLAU and the surrounding conjunctival edges and was complete in 10–18 days. We did not observe any recurrent epithelial defect and/or corneal or conjunctival ulcer during the follow-up period from 15 to 32 months (22.4±6.1 months).
25 23 29 17
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Fig. 2 Key steps of surgical procedure. a Removal of the caruncle: after subconjunctival fibrovascular tissue was thoroughly removed from the sclera extending from the limbus to the superior and inferior fornices, the nasal caruncle was removed by scissors. b AM grafting to limbus and cornea: after 0.02% mitomycin C was applied to the bare sclera and subjacent to the nasal caruncle for 5 min, AM was spread onto the denuded corneal and scleral surface, sutured to the denuded cornea by a 10–0 nylon running suture around the limbus
and the cornea, and to the bared sclera by 10–0 nylon interrupted sutures. c AM grafting to sclera: AM was spread into fornix, caruncle and surrounding conjunctival edges and secured by 10–0 nylon interrupted sutures with episcleral bites. d CLAU grafting: CLAU in the size of 4×6 mm was obtained from the contralateral eye, overlaid on the AM-covered sclera and secured by 10–0 nylon interrupted sutures around the limbus. Arrows indicate the corners of CLAU
For six of seven eyes, the reconstructed fornices were deep, and the distance from the canthus to the limbus was lengthened to that of the contralateral eye. Full ocular motility was recovered, and diplopia at the primary gaze was resolved in six eyes (Fig. 1c, d). In one eye (case 3), persistent conjunctival hyperemia and regrowth of fibrovascular tissue from the nasal caruncle were observed at the 3rd month and reached to the limbus at the 6th month postoperatively (Fig. 1f). This patient still complained of residual diplopia at the lateral gaze, although it was less severe than that before surgery. Not only did this combined approach help prevent recurrence of pterygia, but also the removed fibrovascular membrane over the pupil area, released traction of scar tissue to the cornea and improved ocular surface smoothness, and corneal transparency after surgery contributed to the improvement of visual acuity in all seven eyes, postoperatively (Table 1). Possibly due to previous repeated surgeries, residual corneal scar involving the visual axis was noted in three eyes.
cular tissue even after prior attempts at surgical removal. Previously, Solomon et al. [12] have recognized that it is important to remove thoroughly such subconjunctival fibrovascular tissue, including the semilunar fold, before AMT in order to achieve a low recurrence rate in both primary and recurrent pterygia. We thus carried out a thorough removal of subconjunctival fibrovascular tissues up to the fornices and under the caruncle in all except one case (case 3). The fibrovascular tissue in the caruncle region in case 3 was not removed because that region appeared to be comparatively normal (Fig. 1e). Theoretically, it is not possible to achieve complete removal of subconjunctival fibrovascular tissue, especially in recurrent pterygia, because the inflamed tissue extends deep into the fornix. That was why intraoperative application of MMC was included in our case series. MMC is an alkylating agent that dosedependently and time-dependently inhibits fibroblast proliferation [14]. Intraoperative application of MMC has been successfully used to prevent pterygial recurrences [2, 6]. Although different regimens have been used [2, 6], we chose intraoperative application of 0.02% MMC for 5 min because this regimen achieves a low recurrence rate in primary and recurrent pterygia with few complications in a prospective study [6]. During an average of 22 months follow-up, we have not noted any delayed epithelial healing, recurrent epithelial defect and corneal and scleral
Discussion In our cases, we noted that all these multirecurrent pterygia were associated with abundant subconjunctival fibrovas-
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melting, which were previously reported as complications due to MMC application [1, 8, 13]. This may have contributed to the speedy epithelialization on the denuded scleral and the corneal surface achieved by AMT and CLAU postoperatively. It is generally agreed that the denuded scleral surface is better covered by CAU [5], CLAU [3] or AMT [12] following the thorough removal of primary pterygium. However, in multirecurrent pterygia associated with severe symblepharon, it was not possible to cover the entire denuded scleral surface by CAU alone due to its extraordinary size, reaching one-third to one-half of the ocular surface, created after lysis of symblepharon and extensive removal of subconjunctival fibrovascular tissue. Therefore, AMT become important in these cases to facilitate re-epithelialization. Previously, Solomon et al. [12] still noted that there
was a recurrence rate of 9.5% in treating recurrent pterygia by thorough removal of subconjunctival tissue together with AMT alone. That was why we added CLAU in this study. These combined grafting CLAU over the AM-covered area facilitated the complete epithelialization on the corneal surface in 3–5 days and on the conjunctival surfaces in 10–18 days after surgery. Rapid epithelialization helped reduce inflammation and secure the ocular surface integrity, essential for reducing the recurrence. Obviously, not all pterygia need to be treated with the hitherto described combined approach for multirecurrent pterygia. Future studies are needed to develop a preoperative screening test or a set of clinical profiles to identify those patients who are more susceptible to recurrence so that an ideal surgical procedure can be advised.
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