- Email: [email protected]
Comparison of Fibrin Glue and Sutures for Attaching Conjunctival Autografts After Pterygium Excision
Comparison of Fibrin Glue and Sutures for Attaching Conjunctival Autografts after Pterygium Excision Harvey S. Uy, MD,1,2 Johann Michael G. Reyes, MD,1 John D. G. Flores, MD,1 Ruben Lim-Bon-Siong, MD1 Purpose: To compare the efficacy and safety of fibrin glue and suturing for attaching conjunctival autografts among patients undergoing pterygium excision. Design: Prospective, randomized, interventional case series. Participants: Twenty-two patients undergoing excision of primary pterygium. Methods: A superior conjunctival autograft was harvested and transferred onto bare sclera after pterygium excision. Fibrin glue (Beriplast P) was used to attach the autograft in 11 eyes and nylon 10-0 suture was used to attach the autograft in 11 eyes. The patients were followed up for 2 months. Main Outcome Measures: Graft success, recurrence rate, operating time, patient comfort. Results: All conjunctival autografts in both groups were successfully attached and were intact after 2 months. The average operating time for the fibrin glue group was significantly shorter (P⬍0.001). Postoperative symptoms were fewer for the fibrin glue group than the suture group. One patient (9%) from the fibrin group experienced subconjunctival hemorrhage, and 1 patient (9%) from the suture group experienced partial graft dehiscence. Conclusions: Fibrin glue is a safe and effective method for attaching conjunctival autografts. The use of fibrin glue results in shorter operating times and less postoperative discomfort. Ophthalmology 2005;112:667– 671 © 2005 by the American Academy of Ophthalmology.
The main challenge of pterygium surgery is prevention of recurrence. High recurrence rates have prompted ophthalmologists to develop different adjunctive measures for recurrence prevention. Beta-radiation, excimer laser, and antineoplastic–antimetabolite drugs are some techniques currently used to prevent return of the pterygium, but these may sometimes be associated with serious complications.1–7 Conjunctival autografting after pterygium excision is associated with lower recurrence rates (2%–9%) and relatively few sight-threatening complications.8 –10 The current method of attaching conjunctival autografts is by means of suturing. The use of suture materials requires a high degree of surgical skill and is associated with several disadvantages, including prolonged operating time, postoperative discomfort, and potential for suture-related complications
Originally received: August 30, 2004. Accepted: November 12, 2004. Manuscript no. 2004-62. 1 Department of Ophthalmology and Visual Sciences, University of the Philippines, Philippine General Hospital, Manila, Philippines. 2 Asian Eye Institute, Makati, Philippines. Presented in part at: Association of Researchers in Vision and Ophthalmology Annual Meeting, May, 2002; Fort Lauderdale, Florida. The authors have no financial interest in any of the products or devices mentioned in the article. Correspondence to Harvey S. Uy, MD, Asian Eye Institute, 9F Phinma Plaza Building, Rockwell Center, Makati, Philippines 1200. E-mail: [email protected]. © 2005 by the American Academy of Ophthalmology Published by Elsevier Inc.
such as buttonholes, suture abscesses, granuloma formation, tissue necrosis, and giant papillary conjunctivitis.8 –15 Tissue adhesives are alternative means for attaching conjunctival grafts and may shorten operating time, improve postoperative comfort, and avoid suture-related complications.16,17 This purpose of this study is to compare the efficacy and safety of a preparation of fibrin glue (FG; Beriplast P, Aventis Behring, King of Prussia, PA) with nylon sutures for attaching conjunctival autografts during pterygium surgery.
Patients and Methods Twenty-two consecutive patients with primary pterygia undergoing primary pterygium excision at the Philippine General Hospital from June to August 2001 were prospectively enrolled. A comprehensive medical and ocular history was obtained, including patient age, gender, family, medical and ocular history. Snellen visual acuity measurement, funduscopy, applanation tonometry, slit-lamp examination, and anterior segment photography were performed preoperatively. Patients with ocular pathology other than error of refraction, with a history of previous ocular surgery or trauma, narrow occludable angles, ocular hypertension, physiologic or glaucomatous optic disc cupping, a family history of glaucoma, or known hypersensitivity to any component of FG were excluded. Informed consent was obtained from all patients. The institutional review board approved the protocol and informed consent form. ISSN 0161-6420/05/$–see front matter doi:10.1016/j.ophtha.2004.08.028
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Ophthalmology Volume 112, Number 4, April 2005 Pterygium Grading The pterygia were graded according to the system used by Tan et al:13 grade 1 (atrophic), episcleral vessels under the body of the pterygium are not obscured and clearly distinguished; grade 3 (fleshy), episcleral vessels totally obscured; and grade 2 (intermediate), all other pterygia not falling into these 2 grades.
Fibrin Glue Fibrin glue (Beriplast P) is a fibrin sealant that imitates the final stage of the coagulation process. It is a 2-component system composed of Combiset-1, containing fibrinogen (human), factor XIII (human), and aprotinin (bovine), and Combiset-2, containing thrombin (human) and calcium chloride. Fibrinogen is converted into fibrin on a tissue surface by the action of thrombin. Fibrin is then cross-linked by factor XIII to create a firm, mechanically stable fibrin network. Aprotinin from bovine lungs is present in the fibrin sealant to prevent rapid fibrinolysis. Because the major components of FG, fibrinogen, factor XIII, and thrombin, are isolated from human plasma, potential transmission of contaminants is prevented by screening of plasma donors and donated plasma, virus removal or inactivation by the manufacturing process and pasteurization, and clinical virus safety measures.
Surgical Technique A single surgeon (JGR) performed all surgeries. After instillation of topical proparacaine HCl (Alcaine, Alcon Laboratories, Fort Worth, TX), the involved eye underwent standard ophthalmologic sterile preparation and draping. The pterygia were dissected from the apex using a surgical blade (No. 15) taking care to follow the surgical plane of the pterygium. Dissection was carried to the limbus. A lidocaine– epinephrine solution (Xylocaine 2%, AstraZeneca, Sweden) was then injected into the pterygium head to balloon out the conjunctiva and delineate the underlying fibrovascular tissue. Blunt and sharp dissection was performed to separate the pterygium from the underlying sclera and surrounding conjunctiva. The pterygium head and surrounding atrophic conjunctival edges were then excised with Wescott scissors. The patient was then randomly assigned by coin toss to receive either nylon 10-0 sutures (control group, n ⫽ 11 eyes) or FG (treatment group, n ⫽ 11 eyes). Only 1 eye per patient was entered in the study. For harvesting the free conjunctival autograft, we followed the technique described by Starck et al.9 The conjunctival donor graft site was marked on all sides with gentian violet to outline an oversized graft with an additional 1.0 mm of length and width relative to the dimensions of the graft bed. The epithelial side was marked to prevent graft inversion. The lidocaine– epinephrine solution was injected into the donor conjunctiva to balloon out the area of the graft and separate it from the underlying Tenon’s capsule. By use of minimal manipulation and atraumatic conjunctival forceps and Vannas scissors, the conjunctiva was carefully dissected away from the Tenon’s capsule. Care was taken to prevent buttonholes and graft rollover. The free graft then was placed on top of the cornea and kept moist using sterile normal saline solution irrigating solution. For the suture group, the graft was placed onto the bare sclera, and its 4 corners were anchored to the episclera with nylon 10-0 sutures. Care was taken to maintain the spatial orientation of the graft in relation to the limbus. The limbal side of the graft was affixed to the limbal area with horizontal mattress sutures. The sides of the graft were then attached to the surrounding conjunctiva at intervals of 1 to 1.5 mm with simple interrupted sutures. The sutures were removed 1 month postoperatively.
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In the FG group, a drop of fibrinogen solution was placed on the bare sclera and spread out with a needle cannula. Thrombin solution was applied to activate the sealant. The graft was then immediately transferred onto the bare sclera. Care was taken to ensure that the spatial orientation was maintained and that the sides of the graft were apposed to the edges of the recipient conjunctiva. After a drying period of 5 minutes, the lid retractors were removed, and the patient was asked to blink several times to test graft adherence and mobility. Tobramycin– dexamethasone ointment (TobraDex, Alcon Laboratories, Fort Worth, TX) was placed in all eyes and a pressure patch applied for 24 hours. Tobramycin and dexamethasone eyedrops were applied 6 times daily for 1 month after the surgery.
Study Procedures Operating time was measured starting from placement of the lid retractors to its removal at the end of surgery. The patients were followed up on the first day after surgery and then on weeks 1, 2, 4, and 8. Snellen visual acuity testing and tonometry were tested during each visit. A slit-lamp examination was performed at every visit to monitor autograft integrity and development of complications such as corneal defects, symblepharon formation, giant papillary conjunctivitis, granuloma formation, and contact dermatitis. Graft success was defined as an intact graft by the fourth week after surgery; graft failure was defined as absence of the graft by the fourth week. Recurrence was defined as any growth of conjunctiva into the cornea. Subjective sensations of pain, foreign body sensation, tearing, and discomfort were evaluated on the first postoperative day and on weeks 1, 2, and 4 using a 5-point scale adapted from Lim-BonSiong et al:18 (0) none, no pain; (1) very mild, presence of pain but easily tolerated; (2) mild, pain causing some discomfort; (3) moderate, pain that partially interferes with usual activity or sleep; (4) severe, pain that completely interferes with usual activity or sleep.
Data Analysis Analysis of covariance was used to determine whether there is a difference between the mean operating room time of the FG group and the sutured group. The Friedman test for K-related samples was used to determine differences in pain intensity and other postoperative symptoms.
Results Of the 22 patients, 13 were male (59%). The mean age was 45⫾20 years (range, 23– 67 years). All patients completed the 2-month follow-up period. All pterygia were nasally located. The distribution of pterygium grading was similar for both groups (Table 1). The mean surgical duration was 67.0⫾3.6 minutes for the suture group and 27.8⫾1.0 minutes for the FG group. The mean Table 1. Distribution of Pterygium According to Grading and Treatment Group Pterygium Grade
Suture Group (%)
Fibrin Glue Group (%)
1 (atrophic) 2 (intermediate) 3 (fleshy)
0 (0) 6 (55) 5 (45)
0 (0) 7 (64) 4 (36)
Uy et al 䡠 Fibrin Glue
Degree of pain
4
3 Fibrin glue group Suture group
2
1
0 1
7
14
28
Days after surgery Figure 2. Five-point scale assessment of postoperative pain after conjunctival autografting.
and discomfort were fewer and disappeared more rapidly in the FG group than the suture group. The intensity of these symptoms was significantly lower in the FG group than the suture group on all follow-up days (P⬍0.001). All patients treated with FG were asymptomatic after 2 weeks (Figs 2–5). None of the patients lost vision or had symblepharon develop at the donor site. One patient (9%) in the suture group with a large pterygium blocking the visual axis noted an improvement in Snellen visual acuity from 20/200 to 20/25. One patient in the suture group had partial graft dehiscence develop inferiorly and a conjunctival defect that resolved after 2 weeks. One patient in the FG group had extensive subconjunctival hemorrhage develop under the graft, which spontaneously resolved after 3 weeks, without graft dehiscence.
Figure 1. A, Anterior segment photograph showing preoperative fleshy grade 3 nasal pterygium. B, The same eye 1 day after pterygium excision with intact conjunctival autograft attached with fibrin glue. Fluorescein staining shows epithelial defect corresponding to pterygium site. C, The same eye 1 month after surgery showing complete corneal reepithelialization and a successful conjunctival autograft with markedly less conjunctival congestion and hemorrhage.
operating time was significantly shorter when FG was used instead of nylon sutures (P⬍0.001). Postoperatively, some amount of graft edema and hemorrhage was present in all eyes, and it gradually subsided over time. All grafts were successfully attached and were intact by the end of the follow-up period. There were no cases of pterygium recurrence at the end of the follow-up period (Fig 1). Subjective symptoms of pain, foreign body sensation, tearing,
Figure 3. Five-point scale assessment of postoperative foreign body sensation after conjunctival autografting.
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Ophthalmology Volume 112, Number 4, April 2005
4
Degree of Tearing
3
Fibrin Glue Group Sutured Group
2 1 0 1
7
14
28
Days after surgery Figure 4. Five-point scale assessment of postoperative tearing after conjunctival autografting.
Discussion Pterygium recurrence is the most common complication of pterygium surgery and is a frequent source of frustration for patients and surgeons. The current major methods of recurrence prevention include use of mitomycin C (MMC), conjunctival autografting, and, more recently, amniotic membrane grafting.12,19 A recent meta-analysis of pterygium recurrence after surgery concluded that simple bare sclera resection alone is associated with 6 times higher odds of pterygium recurrence if a conjunctival autograft was not used and 25 times higher odds of recurrence if MMC was not used. The authors recommended that simple bare sclera excision should not be encouraged as a method of primary pterygium removal.2 However, although intraoperative MMC is more effective than -irradiation for prevention of pterygium recurrence, the use of MMC can be associated with sight-threatening complications such as corneoscleral melt, cataract, uveitis, secondary glaucoma, and symblepharon.1,3,5 Conjunctival autografting results in lower pterygium re-
Degree of Discomfort
4
3
F ib rin G lu e G ro u p S u tu re d G ro u p
2
1
0 1
7
14
28
D a ys a fte r s u rg e ry
Figure 5. Five-point scale assessment of subjective postoperative discomfort after conjunctival autografting.
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currence rates compared with bare sclera excision with primary closure and use of amniotic membrane grafts.12 Conjunctival autografting is also associated with fewer complications. Only 1 case of necrotizing scleritis has been reported, and this case responded to steroid treatment.15 Although conjunctival autografting is safer and clearly more effective than bare sclera resection in preventing pterygium recurrence, a greater amount of surgical expertise and technical ability is needed to attach autografts using sutures.14 Furthermore, suture use is associated with patient discomfort and minor complications such as dellen ulcer, symblepharon, and graft dehiscence.11,17 Biologic adhesives, such as FG, offer an alternative method of conjunctival graft attachment that may produce fewer complications and less postoperative discomfort. Fibrin glue has previously been used in ophthalmology for conjunctival wound closure, cataract surgery, oculoplastic and orbital surgery, repair of leaking glaucoma filtering blebs, lamellar keratoplasty, and attachment of an amniotic membrane patch.20 –26 Cohen and MacDonald16 have used an organic tissue adhesive (Tisseel, Baxter, Vienna, Austria) to reduce the number of sutures needed for attaching conjunctival grafts in pterygium surgery. Koranyi et al17 recently completed a randomized clinical trial that demonstrated that FG (Tisseel) alone can be used to attach conjunctival autografts and at the same time reduce operating time and postoperative discomfort. No sight-threatening complications developed, and none of the eyes lost vision in both series. This study compared the use of a different preparation of FG (Beriplast P) with the use of nylon 10-0 sutures for securing conjunctival autografts. All autografts were successfully attached using this preparation. In the study by Koranyi et al,17 Vicryl 7-0 sutures were compared with FG. This study compared FG with nylon 10-0 sutures. Even though nylon 10-0 is a finer material and should produce less suture-related discomfort than Vicryl 7-0, fewer postoperative symptoms were still reported when FG was used for attaching conjunctival autografts. It is clear from these results that grafts attached with FG are better tolerated than grafts attached with suture material. The advantages of using FG include ease of use, shorter operating times, and postoperative comfort. A recent study reported that the success rate of sutured conjunctival autograft can vary widely among different surgeons (range, 5%– 82%). This variability was attributed to significant learning curves and different surgical skill levels among different ophthalmologists.14 Because the use of fibrin glue removes the need for the tedious suturing process, the learning curve can be shortened, and better results may be more consistently achieved despite differences in surgical expertise. Moreover, conjunctival autografting will be better accepted by the patients, because the use of FG produces significantly less symptoms. No recurrences occurred by the end of the 2-month observation period in both treatment groups. However, no conclusions can be made from our data regarding long-term recurrence rates. Because the graft survival rate is similar for both groups, it is expected that the recurrence rates would be similar as well. The short follow-up period is a
Uy et al 䡠 Fibrin Glue limitation of this study, and a long-term study is being planned to determine the recurrence rates and long-term effects of FG in securing conjunctival autografts. There are some concerns regarding the safety of fibrin glue use, including potential for anaphylactic reaction and disease transmission. None of the patients in this study had anaphylactic reactions. Adherence to good manufacturing processes can help avoid transmission of pathogens. Another drawback is the lack of a cost-effectiveness analysis. It would be interesting to investigate whether FG can be used to secure amniotic membrane grafts as well. Fibrin glue (Beriplast-P) comes in a ready-to-use package. The diluent is injected into the corresponding vial containing the lyophilized components. The desired amount of FG component is then drawn off with a sterile syringe needle and is ready for injection. We estimate the preparation time to be 5 minutes or less. The surgical assistant can prepare the FG while the surgeon is excising the pterygium or conjunctival autograft, so that there is no addition to the total operating time. The direct cost of FG was approximately $100 for a 1-ml volume. Our practice was to schedule 5 to 10 pterygium patients on the same day. By use of sterile techniques, several 0.1-ml doses of FG can be readied without crosscontamination. By dividing the 1.0-ml total volume among several patients, the cost can be reduced to $10 to $20 per eye. In summary, FG is an effective and safe method for attaching conjunctival autografts during pterygium surgery. The use of FG can significantly shorten operating times and produce less postoperative symptoms and discomfort. Long-term studies are needed to determine whether the rate of pterygium recurrence is affected by the use of FG instead of suture material.
References 1. Rubinfeld RS, Pfister RR, Stein RM, et al. Serious complications of topical mitomycin-C after pterygium surgery. Ophthalmology 1992;99:1647–54. 2. Sanchez-Thorin JC, Rocha G, Yelin JB. Meta-analysis on the recurrence rates after bare sclera resection with and without mitomycin C use and conjunctival autograft placement in surgery for primary pterygium. Br J Ophthalmol 1998;82: 661–5. 3. Hayasaka S, Noda S, Yamamoto Y, Setogawa T. Postoperative instillation of low-dose mitomycin C in the treatment of primary pterygium. Am J Ophthalmol 1998;106:715– 8. 4. Talu H, Tasindi E, Ciftci F, Yildiz TF. Excimer laser phototherapeutic keratectomy for recurrent pterygium. J Cataract Refract Surg 1998;24:1326 –32. 5. Amano S, Motoyama Y, Oshika T, et al. Comparative study of intraoperative mitomycin C and beta irradiation in pterygium surgery. Br J Ophthalmol 2000;84:618 –21. 6. Dadeya S, Kamlesh, Khurana C, Fatima S. Intraoperative daunorubicin versus conjunctival autograft in primary pterygium surgery. Cornea 2002;21:766 –9. 7. Akarsu C, Taner P, Ergin A. 5-Fluorouracil as chemoadjuvant
8. 9. 10. 11.
12.
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14. 15. 16. 17. 18.
19. 20. 21. 22. 23. 24. 25.
26.
for primary pterygium surgery: preliminary report. Cornea 2003;22:522– 6. Kenyon KR, Wagoner MD, Hettinger ME. Conjunctival autograft transplantation for advanced and recurrent pterygium. Ophthalmology 1985;92:1461–70. Starck T, Kenyon KR, Serrano F. Conjunctival autograft for primary and recurrent pterygia: surgical technique and problem management. Cornea 1991;10:196 –202. Allan BD, Short P, Crawford CJ, et al. Pterygium excision with conjunctival autografting: an effective and safe technique. Br J Ophthalmol 1993;77:698 –701. Chen PP, Ariyasu RG, Kaza V, et al. A randomized trial comparing mitomycin C and conjunctival autograft after excision of primary pterygium. Am J Ophthalmol 1995;120; 151– 60. Prabhasawat P, Barton K, Burkett G, Tseng SC. Comparison of conjunctival autografts, amniotic membrane grafts, and primary closure for pterygium excision. Ophthalmology 1997: 104:974 – 85. Tan DT, Chee SP, Dear KB, Lim AS. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision. Arch Ophthalmol 1997;115:1235– 40. Ti SE, Chee SP, Dear KB, Tan DT. Analysis of variation in success rates in conjunctival autografting for primary and recurrent pterygium. Br J Ophthalmol 2000;84:385–9. Sridhar MS, Bansal AK, Rao GN. Surgically induced necrotizing scleritis after pterygium excision and conjunctival autograft. Cornea 2002;21:305–7. Cohen RA, McDonald MB. Fixation of conjunctival autografts with an organic tissue adhesive [letter]. Arch Ophthalmol 1993;111:1167– 8. Koranyi G, Seregard S, Kopp ED. Cut and paste: a no suture, small incision approach to pterygium surgery. Br J Ophthalmol 2004;88:911– 4. Lim-Bon-Siong R, Valluri S, Gordon M, et al. Efficacy and safety of the ProTek (Vifilcon A) therapeutic soft contact lens after photorefractive keratectomy. Am J Ophthalmol 1998; 125:169 –76. Ma DH, See LC, Liau SB, Tsai RJ. Amniotic membrane graft for primary pterygium: comparison with conjunctival autograft and topical mitomycin C treatment. Br J Ophthalmol 2000;84:973– 8. Zauberman H, Hemo I. Use of fibrin glue in ocular surgery. Ophthalmic Surg 1988;19:132–3. Lagoutte FM, Gauthier L, Comte PR. A fibrin sealant for perforated and preperforated corneal ulcers. Br J Ophthalmol 1989;73:757– 61. Mandel MA. Closure of blepharoplasty incisions with autologous fibrin glue. Arch Ophthalmol 1990;108:842– 4. Bartley GB, McCaffrey TV. Cryoprecipitated fibrinogen (fibrin glue) in orbital surgery. Am J Ophthalmol 1990;109: 227– 8. Kajiwara K. Repair of a leaking bleb with fibrin glue. Am J Ophthalmol 1990;109:599 – 601. Alio JL, Mulet E, Sakla HF, Gobbi F. Efficacy of synthetic and biological bioadhesives in scleral tunnel phacoemulsification in eyes with high myopia. J Cataract Refract Surg 1998;24:983– 8. Kaufman HE, Insler MS, Ibrahim-Elzembely HA, Kaufman SC. Human fibrin tissue adhesive for sutureless lamellar keratoplasty and scleral patch adhesion: a pilot study. Ophthalmology 2003;110:2168 –72.
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The main challenge of pterygium surgery is prevention of recurrence. High recurrence rates have prompted ophthalmologists to develop different adjunctive measures for recurrence prevention. Beta-radiation, excimer laser, and antineoplastic–antimetabolite drugs are some techniques currently used to prevent return of the pterygium, but these may sometimes be associated with serious complications.1–7 Conjunctival autografting after pterygium excision is associated with lower recurrence rates (2%–9%) and relatively few sight-threatening complications.8 –10 The current method of attaching conjunctival autografts is by means of suturing. The use of suture materials requires a high degree of surgical skill and is associated with several disadvantages, including prolonged operating time, postoperative discomfort, and potential for suture-related complications
Originally received: August 30, 2004. Accepted: November 12, 2004. Manuscript no. 2004-62. 1 Department of Ophthalmology and Visual Sciences, University of the Philippines, Philippine General Hospital, Manila, Philippines. 2 Asian Eye Institute, Makati, Philippines. Presented in part at: Association of Researchers in Vision and Ophthalmology Annual Meeting, May, 2002; Fort Lauderdale, Florida. The authors have no financial interest in any of the products or devices mentioned in the article. Correspondence to Harvey S. Uy, MD, Asian Eye Institute, 9F Phinma Plaza Building, Rockwell Center, Makati, Philippines 1200. E-mail: [email protected]. © 2005 by the American Academy of Ophthalmology Published by Elsevier Inc.
such as buttonholes, suture abscesses, granuloma formation, tissue necrosis, and giant papillary conjunctivitis.8 –15 Tissue adhesives are alternative means for attaching conjunctival grafts and may shorten operating time, improve postoperative comfort, and avoid suture-related complications.16,17 This purpose of this study is to compare the efficacy and safety of a preparation of fibrin glue (FG; Beriplast P, Aventis Behring, King of Prussia, PA) with nylon sutures for attaching conjunctival autografts during pterygium surgery.
Patients and Methods Twenty-two consecutive patients with primary pterygia undergoing primary pterygium excision at the Philippine General Hospital from June to August 2001 were prospectively enrolled. A comprehensive medical and ocular history was obtained, including patient age, gender, family, medical and ocular history. Snellen visual acuity measurement, funduscopy, applanation tonometry, slit-lamp examination, and anterior segment photography were performed preoperatively. Patients with ocular pathology other than error of refraction, with a history of previous ocular surgery or trauma, narrow occludable angles, ocular hypertension, physiologic or glaucomatous optic disc cupping, a family history of glaucoma, or known hypersensitivity to any component of FG were excluded. Informed consent was obtained from all patients. The institutional review board approved the protocol and informed consent form. ISSN 0161-6420/05/$–see front matter doi:10.1016/j.ophtha.2004.08.028
667
Ophthalmology Volume 112, Number 4, April 2005 Pterygium Grading The pterygia were graded according to the system used by Tan et al:13 grade 1 (atrophic), episcleral vessels under the body of the pterygium are not obscured and clearly distinguished; grade 3 (fleshy), episcleral vessels totally obscured; and grade 2 (intermediate), all other pterygia not falling into these 2 grades.
Fibrin Glue Fibrin glue (Beriplast P) is a fibrin sealant that imitates the final stage of the coagulation process. It is a 2-component system composed of Combiset-1, containing fibrinogen (human), factor XIII (human), and aprotinin (bovine), and Combiset-2, containing thrombin (human) and calcium chloride. Fibrinogen is converted into fibrin on a tissue surface by the action of thrombin. Fibrin is then cross-linked by factor XIII to create a firm, mechanically stable fibrin network. Aprotinin from bovine lungs is present in the fibrin sealant to prevent rapid fibrinolysis. Because the major components of FG, fibrinogen, factor XIII, and thrombin, are isolated from human plasma, potential transmission of contaminants is prevented by screening of plasma donors and donated plasma, virus removal or inactivation by the manufacturing process and pasteurization, and clinical virus safety measures.
Surgical Technique A single surgeon (JGR) performed all surgeries. After instillation of topical proparacaine HCl (Alcaine, Alcon Laboratories, Fort Worth, TX), the involved eye underwent standard ophthalmologic sterile preparation and draping. The pterygia were dissected from the apex using a surgical blade (No. 15) taking care to follow the surgical plane of the pterygium. Dissection was carried to the limbus. A lidocaine– epinephrine solution (Xylocaine 2%, AstraZeneca, Sweden) was then injected into the pterygium head to balloon out the conjunctiva and delineate the underlying fibrovascular tissue. Blunt and sharp dissection was performed to separate the pterygium from the underlying sclera and surrounding conjunctiva. The pterygium head and surrounding atrophic conjunctival edges were then excised with Wescott scissors. The patient was then randomly assigned by coin toss to receive either nylon 10-0 sutures (control group, n ⫽ 11 eyes) or FG (treatment group, n ⫽ 11 eyes). Only 1 eye per patient was entered in the study. For harvesting the free conjunctival autograft, we followed the technique described by Starck et al.9 The conjunctival donor graft site was marked on all sides with gentian violet to outline an oversized graft with an additional 1.0 mm of length and width relative to the dimensions of the graft bed. The epithelial side was marked to prevent graft inversion. The lidocaine– epinephrine solution was injected into the donor conjunctiva to balloon out the area of the graft and separate it from the underlying Tenon’s capsule. By use of minimal manipulation and atraumatic conjunctival forceps and Vannas scissors, the conjunctiva was carefully dissected away from the Tenon’s capsule. Care was taken to prevent buttonholes and graft rollover. The free graft then was placed on top of the cornea and kept moist using sterile normal saline solution irrigating solution. For the suture group, the graft was placed onto the bare sclera, and its 4 corners were anchored to the episclera with nylon 10-0 sutures. Care was taken to maintain the spatial orientation of the graft in relation to the limbus. The limbal side of the graft was affixed to the limbal area with horizontal mattress sutures. The sides of the graft were then attached to the surrounding conjunctiva at intervals of 1 to 1.5 mm with simple interrupted sutures. The sutures were removed 1 month postoperatively.
668
In the FG group, a drop of fibrinogen solution was placed on the bare sclera and spread out with a needle cannula. Thrombin solution was applied to activate the sealant. The graft was then immediately transferred onto the bare sclera. Care was taken to ensure that the spatial orientation was maintained and that the sides of the graft were apposed to the edges of the recipient conjunctiva. After a drying period of 5 minutes, the lid retractors were removed, and the patient was asked to blink several times to test graft adherence and mobility. Tobramycin– dexamethasone ointment (TobraDex, Alcon Laboratories, Fort Worth, TX) was placed in all eyes and a pressure patch applied for 24 hours. Tobramycin and dexamethasone eyedrops were applied 6 times daily for 1 month after the surgery.
Study Procedures Operating time was measured starting from placement of the lid retractors to its removal at the end of surgery. The patients were followed up on the first day after surgery and then on weeks 1, 2, 4, and 8. Snellen visual acuity testing and tonometry were tested during each visit. A slit-lamp examination was performed at every visit to monitor autograft integrity and development of complications such as corneal defects, symblepharon formation, giant papillary conjunctivitis, granuloma formation, and contact dermatitis. Graft success was defined as an intact graft by the fourth week after surgery; graft failure was defined as absence of the graft by the fourth week. Recurrence was defined as any growth of conjunctiva into the cornea. Subjective sensations of pain, foreign body sensation, tearing, and discomfort were evaluated on the first postoperative day and on weeks 1, 2, and 4 using a 5-point scale adapted from Lim-BonSiong et al:18 (0) none, no pain; (1) very mild, presence of pain but easily tolerated; (2) mild, pain causing some discomfort; (3) moderate, pain that partially interferes with usual activity or sleep; (4) severe, pain that completely interferes with usual activity or sleep.
Data Analysis Analysis of covariance was used to determine whether there is a difference between the mean operating room time of the FG group and the sutured group. The Friedman test for K-related samples was used to determine differences in pain intensity and other postoperative symptoms.
Results Of the 22 patients, 13 were male (59%). The mean age was 45⫾20 years (range, 23– 67 years). All patients completed the 2-month follow-up period. All pterygia were nasally located. The distribution of pterygium grading was similar for both groups (Table 1). The mean surgical duration was 67.0⫾3.6 minutes for the suture group and 27.8⫾1.0 minutes for the FG group. The mean Table 1. Distribution of Pterygium According to Grading and Treatment Group Pterygium Grade
Suture Group (%)
Fibrin Glue Group (%)
1 (atrophic) 2 (intermediate) 3 (fleshy)
0 (0) 6 (55) 5 (45)
0 (0) 7 (64) 4 (36)
Uy et al 䡠 Fibrin Glue
Degree of pain
4
3 Fibrin glue group Suture group
2
1
0 1
7
14
28
Days after surgery Figure 2. Five-point scale assessment of postoperative pain after conjunctival autografting.
and discomfort were fewer and disappeared more rapidly in the FG group than the suture group. The intensity of these symptoms was significantly lower in the FG group than the suture group on all follow-up days (P⬍0.001). All patients treated with FG were asymptomatic after 2 weeks (Figs 2–5). None of the patients lost vision or had symblepharon develop at the donor site. One patient (9%) in the suture group with a large pterygium blocking the visual axis noted an improvement in Snellen visual acuity from 20/200 to 20/25. One patient in the suture group had partial graft dehiscence develop inferiorly and a conjunctival defect that resolved after 2 weeks. One patient in the FG group had extensive subconjunctival hemorrhage develop under the graft, which spontaneously resolved after 3 weeks, without graft dehiscence.
Figure 1. A, Anterior segment photograph showing preoperative fleshy grade 3 nasal pterygium. B, The same eye 1 day after pterygium excision with intact conjunctival autograft attached with fibrin glue. Fluorescein staining shows epithelial defect corresponding to pterygium site. C, The same eye 1 month after surgery showing complete corneal reepithelialization and a successful conjunctival autograft with markedly less conjunctival congestion and hemorrhage.
operating time was significantly shorter when FG was used instead of nylon sutures (P⬍0.001). Postoperatively, some amount of graft edema and hemorrhage was present in all eyes, and it gradually subsided over time. All grafts were successfully attached and were intact by the end of the follow-up period. There were no cases of pterygium recurrence at the end of the follow-up period (Fig 1). Subjective symptoms of pain, foreign body sensation, tearing,
Figure 3. Five-point scale assessment of postoperative foreign body sensation after conjunctival autografting.
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Degree of Tearing
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Fibrin Glue Group Sutured Group
2 1 0 1
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14
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Days after surgery Figure 4. Five-point scale assessment of postoperative tearing after conjunctival autografting.
Discussion Pterygium recurrence is the most common complication of pterygium surgery and is a frequent source of frustration for patients and surgeons. The current major methods of recurrence prevention include use of mitomycin C (MMC), conjunctival autografting, and, more recently, amniotic membrane grafting.12,19 A recent meta-analysis of pterygium recurrence after surgery concluded that simple bare sclera resection alone is associated with 6 times higher odds of pterygium recurrence if a conjunctival autograft was not used and 25 times higher odds of recurrence if MMC was not used. The authors recommended that simple bare sclera excision should not be encouraged as a method of primary pterygium removal.2 However, although intraoperative MMC is more effective than -irradiation for prevention of pterygium recurrence, the use of MMC can be associated with sight-threatening complications such as corneoscleral melt, cataract, uveitis, secondary glaucoma, and symblepharon.1,3,5 Conjunctival autografting results in lower pterygium re-
Degree of Discomfort
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3
F ib rin G lu e G ro u p S u tu re d G ro u p
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0 1
7
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D a ys a fte r s u rg e ry
Figure 5. Five-point scale assessment of subjective postoperative discomfort after conjunctival autografting.
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currence rates compared with bare sclera excision with primary closure and use of amniotic membrane grafts.12 Conjunctival autografting is also associated with fewer complications. Only 1 case of necrotizing scleritis has been reported, and this case responded to steroid treatment.15 Although conjunctival autografting is safer and clearly more effective than bare sclera resection in preventing pterygium recurrence, a greater amount of surgical expertise and technical ability is needed to attach autografts using sutures.14 Furthermore, suture use is associated with patient discomfort and minor complications such as dellen ulcer, symblepharon, and graft dehiscence.11,17 Biologic adhesives, such as FG, offer an alternative method of conjunctival graft attachment that may produce fewer complications and less postoperative discomfort. Fibrin glue has previously been used in ophthalmology for conjunctival wound closure, cataract surgery, oculoplastic and orbital surgery, repair of leaking glaucoma filtering blebs, lamellar keratoplasty, and attachment of an amniotic membrane patch.20 –26 Cohen and MacDonald16 have used an organic tissue adhesive (Tisseel, Baxter, Vienna, Austria) to reduce the number of sutures needed for attaching conjunctival grafts in pterygium surgery. Koranyi et al17 recently completed a randomized clinical trial that demonstrated that FG (Tisseel) alone can be used to attach conjunctival autografts and at the same time reduce operating time and postoperative discomfort. No sight-threatening complications developed, and none of the eyes lost vision in both series. This study compared the use of a different preparation of FG (Beriplast P) with the use of nylon 10-0 sutures for securing conjunctival autografts. All autografts were successfully attached using this preparation. In the study by Koranyi et al,17 Vicryl 7-0 sutures were compared with FG. This study compared FG with nylon 10-0 sutures. Even though nylon 10-0 is a finer material and should produce less suture-related discomfort than Vicryl 7-0, fewer postoperative symptoms were still reported when FG was used for attaching conjunctival autografts. It is clear from these results that grafts attached with FG are better tolerated than grafts attached with suture material. The advantages of using FG include ease of use, shorter operating times, and postoperative comfort. A recent study reported that the success rate of sutured conjunctival autograft can vary widely among different surgeons (range, 5%– 82%). This variability was attributed to significant learning curves and different surgical skill levels among different ophthalmologists.14 Because the use of fibrin glue removes the need for the tedious suturing process, the learning curve can be shortened, and better results may be more consistently achieved despite differences in surgical expertise. Moreover, conjunctival autografting will be better accepted by the patients, because the use of FG produces significantly less symptoms. No recurrences occurred by the end of the 2-month observation period in both treatment groups. However, no conclusions can be made from our data regarding long-term recurrence rates. Because the graft survival rate is similar for both groups, it is expected that the recurrence rates would be similar as well. The short follow-up period is a
Uy et al 䡠 Fibrin Glue limitation of this study, and a long-term study is being planned to determine the recurrence rates and long-term effects of FG in securing conjunctival autografts. There are some concerns regarding the safety of fibrin glue use, including potential for anaphylactic reaction and disease transmission. None of the patients in this study had anaphylactic reactions. Adherence to good manufacturing processes can help avoid transmission of pathogens. Another drawback is the lack of a cost-effectiveness analysis. It would be interesting to investigate whether FG can be used to secure amniotic membrane grafts as well. Fibrin glue (Beriplast-P) comes in a ready-to-use package. The diluent is injected into the corresponding vial containing the lyophilized components. The desired amount of FG component is then drawn off with a sterile syringe needle and is ready for injection. We estimate the preparation time to be 5 minutes or less. The surgical assistant can prepare the FG while the surgeon is excising the pterygium or conjunctival autograft, so that there is no addition to the total operating time. The direct cost of FG was approximately $100 for a 1-ml volume. Our practice was to schedule 5 to 10 pterygium patients on the same day. By use of sterile techniques, several 0.1-ml doses of FG can be readied without crosscontamination. By dividing the 1.0-ml total volume among several patients, the cost can be reduced to $10 to $20 per eye. In summary, FG is an effective and safe method for attaching conjunctival autografts during pterygium surgery. The use of FG can significantly shorten operating times and produce less postoperative symptoms and discomfort. Long-term studies are needed to determine whether the rate of pterygium recurrence is affected by the use of FG instead of suture material.
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