Conjunctivolimbal Autograft Using A Fibrin Adhesive in Pterygium Surgery
Conjunctivolimbal Autograft Using A Fibrin Adhesive in Pterygium Surgery
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Purpose: To evaluate the efficacy and safety of fibrin bioadhesive in conjunctivolimbal autograft surgery for
primary pterygium.
Methods: Thirty-six eyes in 34 patients were reviewed with nasal primary pterygium who were treated with
pterygium excision with superior conjunctivolimbal transplantation with fibrin bioadhesive. Surgical durations
were recorded and the patients were followed up on the first day after surgery and then at 1, 2, 4, 8 and
12 weeks postoperatively. The graft-recipient site attachments were examined and subjective symptoms of
patients were recorded at every follow-up examinations.
Results: The mean patient age was 57.9±10.1 (ranging from 33 to 83) years. The mean follow-up period
was 22.05±5.78 weeks. The mean surgery time was 18.04±5.65 minutes. The subjective symptoms (pain,
foreign body sensation, tearing and discomfort) disappeared in 23 of 36 eyes (64%) in one week after
surgery, and all discomforts subsided within two weeks after surgery in all patients. The conjunctivolimbal
autograft was correctly positioned and fixed in 34 of 36 eyes (94.4%) throughout the follow-up period. Graft
dehiscence was seen in two eyes (5.6%), one eye was treated with remedial sutures, and the other eye
showed a spontaneous healing without remedial sutures. Transient graft edema occurred in four eyes
(11.2%) but subsided spontaneously within a month. There were no cases of pterygium regrowth or
complications due to the fibrin bioadhesive.
Conclusions: The use of fibrin bioadhesive in conjunctivolimbal autograft surgery in primary pterygium
simplifies surgical techniques, shorten surgical duration, and produce less postoperative subjective
symptoms . Therefore, the fibrin bioadhesive is a safe and effective tool to attach conjunctivolimbal autograft
in primary pterygium surgery.
Korean J Ophthalmol 2008;22:147-154 ⓒ 2008 by the Korean Ophthalmological Society.
Pterygium, a common ocular surface disorder, is a triangular recurrence rate have discrepancies, but the recurrence rate of
-shaped growth of bulbar conjunctival epithelium and primary pterygium after simple excision is reportedly
hypertrophied subconjunctival connective tissue in the medial 25-45%.2 Subsequently, some techniques currently used to
and lateral palpebral fissure encroaching onto the cornea. prevent recurrence of pterygium are beta-radiation, excimer
Well-known risk factors are genetic predisposition, immune laser, argon laser, Thio-Tepa and anti-metabolite drugs,
mechanism and chronic environmental irritations including conjunctivolimbal autograft and amniotic membrane graft.3-10
ultraviolet rays, wind, and dusts, even though the etiology The recurrence of pteygium is closely associated with
remains not clearly known.1 The prime challenge of corneo-limbal stem cell deficiency. The recurrent pterygium
pterygium surgery is prevention of recurrence. The reports of is usually associated with more severe conjunctival inflam-
mation, corneal involvement, and adhesion with surrounding
tissue than the primary pterygium, causing conjunctival
Received: April 10, 2008 Accepted: August 11, 2008 injection, ocular pain, ocular movement dysfunction and
diplopia.
Reprint requests to Young Jeung Park, MD. Department of Ophthal- Anti-metabolites including mitomycin C (MMC) were
mology, Cheil Eye Hospital, 803-2 Sinam-dong, Dong-gu, Daegu
701-011, Korea. Tel: 82-53-959-1751, Fax: 82-53-959-1758, E-mail:
introduced to prevent the recurrence of pterygium. The use
eyepark9@dreamwiz.com of anti-metabolites is restricted by several complications
including various ocular surface diseases, secondary glaucoma,
* This study was presented in part at the 97th Annual meeting of and cataract.7
the Korean Ophthalmological Society, April, 2007 and the American
Society of Cataract and Refractive Surgery, April, 2007.
The transplantation of conjunctival or conjunctivolimbal
147
Korean J Ophthalmol Vol.22, No.3, 2008
autograft was reported to be the most effective method of distinguished; grade 3 (fleshy), episcleral vessels totally
lowering recurrence rate (2~9%) and occurrence of obscured; and grade 2 (intermediate), and all other pterygia
9-11
complications. not falling into these 2 grades (Table 1).
However, the current method of attaching conjunctival or
conjunctivolimal autograft by means of suturing presents Fibrin Bioadhesive
several disadvantages, including complicated surgical
®
techniques, prolonged operating time, prolonged postope- Fibrin glue (Tissucol Duo Quick ) is a tissue adhesive
rative patient discomfort, and suture-related potential composed of two components which mimics the natural fibrin
complications. Moreover, many Asian patients, including formation. One component contains fibrinogen mixed with
Koreans, have narrower interpalpebral fissures than coagulation factor 13 and aprotinin, and the other component
Caucasians or Africans, which can make suturing procedures contains thrombin and calcium chloride. Once the two
more difficult to attach the conjunctival or conjunctivolimbal components are mixed, fibrinogen is converted into fibrin by
autograft. the action of thrombin; fibrin is then cross-linked by
Fibrin tissue bioadhesives which mimics the natural coagulation factor 13 to create a firm fibrin network.
fibrinogen and thrombin reaction are used on various Aprotinin from bovine lungs prevent rapid fibrinolysis.
ophthalmologic surgeries for tissue adhesion, blood
12-18
coagulation and wound healing. The use of tissue Surgical Technqiue
bioadhesives as an alternative means of attaching the grafts
may shorten operating time, improve postoperative A single surgeon (Y.J. Park) performed all surgeries
16-18
discomfort, and possibly avoid suture-related complications. according to the same surgical techniques (Fig. 1). After
®
The purpose of this study is to reveal the efficacy and instillation of topical proparacaine HCl (Alcaine , Alcon
®
safety of using fibrin bioadhesive (Tissucol Duo Quick , Laboratories, Fort Worth, TX), the involved eye underwent
Baxter AG, Vienna, Austria) in place of sutures during standard ophthalmologic sterile preparation and draping.
conjunctivolimbal autograft surgery for primary pterygium in Then, the eye was exposed for operation using lid speculum.
®
Korean patients. A lidocaine–epinephrine solution (Xylocaine 2%, Astra-
Zeneca, Sweden) was injected into the pterygium head to
Materials and Methods balloon out the conjunctiva. Blunt and sharp dissection was
performed to separate the pterygium from the underlying
From March to October, 2006, 36 eyes in 34 patients (a sclera and surrounding conjunctiva. The pterygium head and
consecutive case series) with nasal primary pterygium were surrounding atrophic conjunctival edges were excised and
treated with superior conjunctivolimbal transplant with fibrin sclera was exposed. MMC was not used during or after the
glue (Tissucol Duo Quick®) at Cheil Eye Hospital by a single operation.
surgeon. Informed consent was obtained from all patients. Before harvesting the free conjunctivolimbal autograft
Before surgery, a comprehensive investigation was taken from superior limbus, the lidocaine-epinephrine solution was
including patient age, gender, medical and ocular history. injected in to the donor conjunctiva to balloon out the area
Snellen visual acuity measurement, non-contact tonometry of the graft and separate it from the underlying Tenon’s
(Canon TX-10 tonometer), slit-lamp examination, and anterior capsule. The donor graft at superior limbus was excised with
segment photography were performed preoperatively. Patients an additional 1.0 mm of length and width relative to the
with ocular pathology other than refractive error such as dimensions of the graft bed. By use of minimal manipulation
history of previous ocular surgery or trauma and known with atraumatic conjunctival forceps and Vannas scissors, the
hypersensitivity to any component of fibrin bioadhesive were conjunctiva was carefully dissected away from the Tenon’s
excluded. capsule. Care was taken to prevent buttonholes and graft
rollover. The dissected graft was flipped over the cornea, and
Pterygium Grading then taking care that the palisades of Vogt was included in
the graft, excision was made from limbal attachment. The
The pterygia were graded according to the system used by free graft then was placed on top of the cornea and kept
Tan et al.11: grade 1 (atrophic), episcleral vessels under the moist.
body of the pterygium are not obscured and clearly A drop of fibrinogen solution was placed on the bare
11
Table 1. Pterygium grading system suggested by Tan et al.
Grade 1 (atrophic) Episcleral vessels under the body of the pterygium not obscured and clearly distinguished
Grade 2 (intermediate) All other pterygia not falling into grade 1 or 3
Grade 3 (fleshy) Episcleral vessels totally obscured by the body of pterygium
148
HH Kim, et al. CONJUNCTIVAL AUTOGRAFT WITH BIOADHESIVE IN PTERYGIUM
Fig. 1. Surgical procedures of conjunctivolimbal autograft using a fibrin adhesive (Tissucol Duo Quick®) in pterygium surgery.
(A) Pre-operative fleshy nasal pterygium. (B) The pterygium head was excised, the conjunctiva allowed to retract, and the
subconjunctival fibrovascular tissue excised en bloc. (C) Superior conjunctivolimbal autograft was flipped over the cornea and the
limbal attachment, and them the head of the palisades of Vogt was cleaned with a blade. (D) Conjunctivolimbal autograft kept placed
over the cornea. The graft was rotated toward the defect site, spreading the conjunctiva out, being mindful of orienting the limbal stem
cell population toward the limbus. (E) The fibrin glue was applied over the bare sclera and conjunctivolimbal autograft; A drop of
fibrinogen solution was placed on the bare sclera and a drop of thrombin solution was placed conjunctivolimbal autograft.
(F) Conjunctivolimbal autograft spread over the bare sclera with the edges bonded to the surrounding health conjunctiva by using
McPherson forceps.
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Korean J Ophthalmol Vol.22, No.3, 2008
Fig. 3. Left column (A, B, C, D, E, F): Images of preoperative fleshy grade 3 nasal primary pterygium. Right column (G, H, I, J,
K, L): Images of the conjuntivolimbal autograft of the same patients on 12 weeks after surgery. Well-positioned graft and
reestablishment of the normal limbal architecture are observed with no signs of recurrence in all subjects.
150
HH Kim, et al. CONJUNCTIVAL AUTOGRAFT WITH BIOADHESIVE IN PTERYGIUM
A B
Fig. 4. (A) Mild shrinkage (between arrows) of the conjunctivolimbal autograft and recipient conjunctiva was noted 2 weeks after
surgery: Secondary epithelialization and spontaneous closure of the wound gap occurred in one week. (B) Transient edema (arrows)
of conjunctivolimbal autograft 2 weeks after surgery: Spontaneous resolution occurred in one month.
In 34 of 36 (94.4%) cases, the conjunctivolimbal autograft associated with fewer complications compared to use of
was observed to be correctly positioned and fixed in all the MMC.20 Only one case of necrotizing scleritis has been
follow-up exams (Fig. 2, 3). Graft dehiscence was observed reported, and that case was successfully treated with steroid
in two eyes (5.6%), one eye was given remedial sutures, and treatment.21 But, conjunctival autografting leaves conjunctival
the other eye showed spontaneous healing without remedial defects and adhesions due to fibrosis on the donor site,
sutures after a week. Transient graft edema occurred in four adding to the technical difficulty of another ocular surgeries,
eyes (11.2%) but spontaneously subsided within a month especially glaucoma surgery.2.22
(Fig. 4). There were no cases of pterygium regrowth or Due to these problems, amniotic membrane transplantation
complications due to the fibrin bioadhesive during the has been suggested a replacement for conjunctival auto-
follow-up period. grafting in several studies. Amniotic membrane is the
innermost layer of fetal membrane composed of thick
D iscussion basement membrane and monolayer epithelium. The amniotic
membrane functions as a barrier to protect fetus from the
Preventing pterygium recurrence is the main concern of maternal infection and immune mechanisms. In addition,
pterygium surgery. The current major methods to prevent amniotic membrane transplantation causes no rejections.28
recurrence include use of MMC, conjunctival autografting, The basement membrane of amniotic membrane promotes the
19
and amniotic membrane grafting. The meta-analysis of differentiation and migration of epithelial cells and reinforce
pterygium recurrence after surgery reported by Sanchez- the attachment of basal epithelial cells.29 Several growth
10
Thorin et al. concluded that simple bare sclera resection factors and anti-proteolytic factors from aminiotic membrane
alone is associated with 6 times higher odds of pterygium suppress the death and apoptosis of corneal surface cells;30
recurrence when MMC was used compared with conjunctival hence, it is used for the treatment of various ocular surface
autograft, and 25 times higher odds of recurrence if MMC diseases. But in reality, amniotic membrane transplantation
was not used. The authors, therefore, recommended that showed no reduction of recurrences in pterygium surgery
simple bare sclera excision should not be encouraged as a compared to simple bare sclera technique. Amniotic
10
method of primary pterygium removal. Although the membrane transplantation also had higher recurrence rate of
intraoperative use of MMC is effective in preventing pterygia compared to conjunctival autografting according to
pterygium recurrence, the use of MMC can be associated several studies.9,19,26,31
with sight-threatening complications such as corneoscleral As stated, conjunctival autografting is safe and clearly
melt, cataract, uveitis, secondary glaucoma, and symble- effective method in preventing pterygium recurrence, but in
3,7-10
pharon. addition to the donor site conjunctival defects, the technical
According to several scientific papers so far, conjunctival difficulty of attaching the autograft and prolonged operation
autografting results in lower pterygium recurrence rates when time with suturing can be a challenge for many
9-11,20-27
compared with bare sclera excision and it is also surgeons.11,20-22 Furthermore, suture use is associated with
151
Korean J Ophthalmol Vol.22, No.3, 2008
patient discomfort (foreign body sensation, pain, discomfort, conjunctivolimbal autografting in lowering recurrence of
and tearing) and minor complications such as dellen ulcer, pterygium to simple conjunctival autografting in tissue
18
symblepharon, and graft dehiscence. reconstruction.
The transplantation of autologous conjunctiva can be Biologic adhesives, such as fibrin glue, can be an
divided into the simple conjunctival autograft and the alternative method of conjunctival or conjunctivolimbal graft
conjunctivolimbal autograft including the corneal limbus. attachment that may produce fewer complications and less
23
Guler et al. reported a 13.3% recurrence rate in the seven postoperative discomforts. Fibrin glue has previously been
cases followed for 14 to 24 months after conjunctivolimbal used in ophthalmology for conjunctival wound closure,
autografting in recurrent pterygium. The authors hypothesized cataract surgery, oculoplastic and orbital surgery, repair of
the merit of conjunctivolimbal autografting including palisades leaking glaucoma filtering blebs, lamellar keratoplasty, and
12-18
of Vogt superior to simple conjunctival autografting in attachment of amniotic membrane patch.
24 16
histologic structure reconstruction. Polute et al. reported the Cohen and MacDonald have reported the utility of an
®
efficacy of conjunctivolimbal autografting in preventing the organic tissue adhesive (Tisseel , Baxter, Vienna, Austria)
recurrence of pterygia the first several years after long-term used to reduce the number of sutures needed for attaching
22 17
follow-up study over an average 44.97 months. Kim et al. conjunctival grafts in pterygium surgery. Koranyi et al.
reported a 1.9% recurrence rate 15 months after reported a randomized clinical trial that demonstrated that
®
conjunctivolimbal autografting without MMC use in patients fibrin glue (Tisseel ) alone without suture can be used
25
under age 40 with primary pterygium. Ahn et al. reported successfully to attach conjunctival autografts and at the same
no recurrences for 5 to 16 months after conjunctivolimbal time reduce operating time and postoperative discomforts
18
autografting combined with the use of MMC in 10 cases of compared with vicryl 7-0 sutures. Harvey et al. also reported
recurrent pterygium. This study also showed no recurrence of a randomized clinical trial to show the advantage of fibrin glue
®
pterygium for 22.0±5.8 weeks follow-up after conjunctivo- (Beriplast P , Aventis Behring, King of Prussia, PA) compared
limbal autografting including the palisades of Vogt. Despite to suturing with nylon 10-0 for attaching conjunctival limbal
the relative brevity of follow-up period, there was no autograft after pterygium excision. No sight-threatening
recurrence of pterygium and no differences in recurrence rate complications developed, and none of the eyes lost vision in
according to the pterygium grade. Nevertheless, more studies both series. Vicryl 7-0 sutures were compared with fibrin glue
17
are required to prove clinical merits of superiority of in the study by Koranyi et al. and nylon 10-0 sutures
152
HH Kim, et al. CONJUNCTIVAL AUTOGRAFT WITH BIOADHESIVE IN PTERYGIUM
18
compared with fibrin glue in the study by Harvey et al. fewer Korean Ophthalmol Soc 1987;28:933-7.
postoperative symptoms were reported when fibrin glue was 2. Allan BDS, Short P, Crawford GJ, et al. Pinguecula and
17,24 pterygia. Surv Ophthalmol 1988;32:41-9.
used for attaching conjunctival autografts in both studies.
3. Amano S, Motoyama Y, Oshika T, et al. Comparative
These reports showed that grafts attached with fibrin glue are study of intraoperative mitomycin C and beta irradiation in
better tolerated than grafts attached with suturing. pterygium surgery. Br J Ophthalmol 2000;84:618-21.
The advantages of using fibrin glue for attaching graft 4. Talu H, Tasindi E, Ciftci F, Yildiz TF. Excimer laser
include ease of use, shorter operating times, and less phototherapeutic keratectomy for recurrent pterygium. J
Cataract Refract Surg 1998;24:1326-32.
postoperative discomforts. This study showed the reduction
5. Na KS, Kim JY, Choi, GJ. A clinical observation on the
of mean operation time compared to that of conjunctival or argon laser effect of the pterygium. J Korean Ophthalmol
conjunctivolimbal autografting attached with suturing in other Soc 1996;37:1120-5.
studies (Table 3). A recent study by Ti et al. reported that 6. Joselson GA, Muller VP. Incidence of pterygium recurrence
the success rate of sutured conjunctival or conjunctivolimbal in patients treated with Thio-tepa. Am J Ophthalmol
1966;81:891-5.
autograft can vary widely among different surgeons (range,
21 7. Panda A, Gopal KD, Suhas W, et al. Randomized trial of
5%–82%). This variability was probably attributed to intaoperative mitomycin C in surgery for pterygium. Am J
different surgical skill levels on learning curves among Ophthalmol 1998;125:59-63.
different ophthalmologists. Because the use of fibrin glue 8. Rubinfeld RS, Pfister RR, Stein RM, et al. Serious
removes the need for the tedious suturing process, the complications of topical mitomycin-C after pterygium
surgery. Ophthalmology 1992;99:1647-54.
learning curve can be shortened, and better results may be
9. Ma DH, See LC, Liau SB, Tsai RJ. Aminotic membrane
more consistently achieved despite differences in surgical graft for primary pterygium: comparision with conjunctival
expertise. Moreover, conjunctival or conjunctivolimbal autograft and topical mitomycin C treatment. Br J
autografting will be better accepted by the patients, because Ophthalmol 2000;84:973-8.
the use of fibrin glue produces less subjective symptoms as 10. Sanchez-Thorin JC, Rocha G, Yelin JB. Meta-analysis on
the recurrence rates after bare sclera resection with and
shown when comparing of postoperative subjective symptoms
without mitomycin C use and conjunctival autograft
in other studies (Table 4). In this study, only inquiry placement in surgery for primary pterygium. Br J
regarding the presence and duration of subjective symptoms Ophthalmol 1998;82:661-5.
(foreign body sensation, pain, discomfort, and tearing) was 11. Tan DT, Chee SP, Dear KB, Lim AS. Effect of pterygium
made, not 5-point scale self-evaluation used in studies by morphology on pterygium recurrence in a contolled trial
18 comparing conjunctival autografting with bare sclera
Harvey et al. due to the poor communication capability of
excision. Arch Ophthalmol 1997;115:1235-40.
a considerable numbers of the subjects. If 5-point scale 12. Lagoutte FM, Gauthier L, Comte PR. A fibrin sealant for
self-evaluation was adopted in this study, more objective perforated and preperforated corneal ulcers. Br J
results could have been expected. Ophthalmol 1989;73:757-61.
All autografts were successfully attached in this study. 13. Mandel MA. Closure of blepharoplasty incisions with
autologous fibrin glue. Arch Ophthalmol. 1990;108:842-4.
Wound gapping in two eyes (5.6%) and transient graft edema
14. Kajiwara K. Repair of a leaking bleb with fibrin glue. Am
in four eyes (11.2%) were observed, but no critical J Ophthalmol 1990;109:599-601.
complications due to fibrin glue were observed including 15. Kaufman HE, Insler MS, Ibrahim-Elzembely HA, Kaufman
corneal defects, symblepharon, giant papillary conjunctivitis, SC. Human fibrin tissue adhesive for sutureless lamellar
granulation and contact dermatitis, previously proposed in keratoplasty and scleral patch adhesion: a pilot study.
11,20,22 Ophthalmology 2003;110:2168-72.
other studies as possible complications.
16. Cohen RA, McDonald MB. Fixation of conjunctival
There are some concerns regarding the safety of fibrin glue autografts with an organic tissue adhesive. Arch Ophthalmol
use, including potential for anaphylactic reaction and disease 1993;111:1167-8.
18
transmission. None of the patients in this study had 17. Koranyi G, Seregard S, Kopp ED. Cut and paste: a no
anaphylactic reactions. Adherence to strict manufacturing suture, small incision approach to pterygium surgery. Br J
Ophthalmol 2004;88:911-4.
processes can prevent transmission of pathogens.
18. Harvey SU, Reyes JM, Flore JD, Lim-Bon-Siong R.
In summary, fibrin glue is an effective and safe method Comparison of fibrin glue and sutures for attaching
for attaching conjunctival or conjunctivolimbal autografts conjunctival autografts after pterygium excision. Ophthal-
during pterygium surgery. The use of fibrin glue can ease the mology 2005112:667-71.
surgical procedures, shorten operating times and produce less 19. Kim JC, Lee DH, Shyn KH. Clinical use of human
amniotic membrane for ocular surface diseases. Advances in
postoperative symptoms and discomfort. However, long-term
Corneal Research 1997:117-34.
postoperative studies are needed to confirm whether the rate 20. Sridhar MS, Bansal AK, Rao GN. Surgically induced
of pterygium recurrence and other complications are affected necrotizing scleritis after pterygium excision and
by the use of fibrin glue. conjunctival autograft. Cornea 2002;21:305-7.
21. Ti SE, Chee SP, Dear KB, Tan DT. Analysis of variation
in success rates in conjunctival autografting for primary and
References recurrent pterygium. Br J Ophthalmol 2000;84:385-9.
22. Kim YS, Kim JH, Byun YJ. Limbal-conjunctival autograft
1. Lee SH, Jeong HJ. Immune reactions in pterygium. J transplantation for the treatment of primary pterygium. J
153
Korean J Ophthalmol Vol.22, No.3, 2008
Korean Ophthalmol Soc 1999;40:1804-10. autograft for recurrent pteygium. J Korean Ophthalmol Soc
23. Guler M, Sobaci G, Liker S, et al. Limbal-conjunctival 1994;35:1335-9.
autograft transplantation in cases with recurrent pterygium. 28. Van Herendael BJ, Oberti C, Brosens I. Microanatomy of
Acta Ophthalmologica 1994;72:721-6. the human amniotic membrane: a light microscopic,
24. Polute P, Heilinggenhaus A, Koch J, Steuhl KP. Long-term transmission, and scanning microscopic study. Am J Obstet
results of autologous conjunctival-limbus transplantation in Gynecol 1978;131:872-80.
pterygium. Klin Monatsbl Augenheilkd 1998;213:9-14. 29. Terranova VP, Lyall RM. Chemotaxis of human gingival
25. Ahn DG, Auh SJ, Choi YS. The clinical results of limbal epithelial cells to laminin: a mechanism for epithelial cell
conjunctival transplantation with intraoperative mitomycin apical migration. J Periodontol 1986;57:311-7.
C application for recurrent pterygium. J Korean Ophthalmol 30. Na BK, Hwang JH, Kim JC, et al. Analysis of human
Soc 1999;40:2443-9. amniotic membrane components as proteinase inhibitors for
26. Park JM, Ahn HB, Park WC. The effect of combined development of therapeutic agent for recalcitrant keratitis.
amniotic membrane and limbal transplantation for recurrent Tropho Res 1999l;13:453-66.
pterygium or pseudopterygium. J Korean Ophthalmol Soc 31. Kim MJ, Tchah HW. Treatment of pterygium with amniotic
2003;44:1504-11. membrane transplantation. J Korean Ophthalmol Soc
27. Oh TH, Choi GY, Yoon BJ. The effect of conjunctival 1998;39:59-64.
154