CLINICAL SCIENCE
Outcomes of Fibrin Glue-Assisted Conjunctival Versus Conjunctivolimbal Autograft in Primary Pterygia With a New Technique of Conjunctival Resection and Tenon Extended Removal Chintan Malhotra, MS, Arun K. Jain, MD, Ashish Sawhney, MS, Nishant Nawani, MS, and Jagat Ram, MS
Purpose: The aim of this study was to compare the recurrence rates
for primary pterygia after fibrin glue–assisted conjunctival autograft (CAG) versus conjunctivolimbal autograft (CLAG) transplantation, using a technique of limited conjunctival resection and Tenon extended removal.
Method: In this comparative case series, 49 eyes of 47 patients with primary nasal pterygium were included. Patients were randomized into 2 groups to undergo fibrin glue–assisted CAG (group 1, 24 eyes) or fibrin glue–assisted CLAG (group 2, 25 eyes) following excision of pterygium. The surgical technique used in all patients involved limited conjunctival resection combined with extensive removal of the Tenon capsule up to the caruncle medially and also 5 mm beyond the inferior and superior free edges of the conjunctiva. The main outcome measure studied was the absence or presence of recurrence. Results: There was 0% recurrence rate in both groups after a mean follow-up of 63 weeks (range, 54–81 weeks) with all eyes completing at least 1-year of follow-up. Conclusions: Fibrin glue–assisted CAG and CLAG using the technique of conjunctival resection and Tenon extended removal were equally efficacious in terms of preventing recurrences in patients with primary pterygia in our series. Key Words: pterygium, conjunctival autograft, conjunctivolimbal autograft (Cornea 2015;34:193–198)
P
terygium is a common degenerative condition found most commonly in the “pterygium area,” defined by geographical boundaries of 40-degree latitudes north and south of the equator.1 In these areas, prevalence of up to 22% has been Received for publication June 22, 2014; revision received October 9, 2014; accepted October 13, 2014. Published online ahead of print December 3, 2014. From the Advanced Eye Centre, Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. The authors have no funding or conflicts of interest to disclose. Reprints: Arun K. Jain, MD, Advanced Eye Centre, Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Room No. 110, Chandigarh 160012, India (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
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reported,1,2 whereas elsewhere, reported prevalence rates usually do not exceed 2% of the general population. Indications for removal of pterygium include decreased vision that may be either due to proximity of pterygium to the visual axis or induced astigmatism, restriction of ocular movements, and cosmesis. Despite a wide variety of surgical techniques that have been described for its management ranging from simple resection or bare sclera technique to avulsion, removal and primary closure, pterygium head transplantation, concomitant beta radiation, conjunctival autograft (CAG), conjunctivolimbal autograft (CLAG), and use of amniotic membrane with/without conjunctival graft3–7 prevention of recurrences still remains a challenge. Recurrence rates varying from as low as 2% to up to 80% have been recorded, depending on the surgical technique used.3 Transplantation of CAG or CLAG has been reported to be the most effective method of lowering recurrence rates and occurrence of complications.8,9 The rationale for including limbal tissue was based on certain theories, which suggested that the healthy limbal epithelium acts as a junctional barrier to conjunctival migration onto the corneal surface.10,11 Also, pterygium has been speculated to represent “local limbal deficiency.”12 As a consequence, it has been assumed that inclusion of limbal epithelium in the conjunctival graft for pterygium surgery would achieve better anatomic and functional outcomes by restoring the barrier function of the limbus. Recurrence rates of 2% to 39% for CAG9,13–17 and 0% to 18% for CLAG7,18–20 have been reported by previous investigators. Previous studies directly comparing the 2 techniques have included patients with both primary and recurrent pterygia,18,21 or recurrent pterygia only,22 with mitomycin C also being used as an adjuvant by Kheirkhah et al.21 As no unanimity of opinion exists as to which technique is better, this study was designed to directly compare prospectively and report our experience with the outcomes of fibrin glue–assisted CAG and CLAG for primary pterygia, using a technique of limited conjunctival resection combined with extended removal of the Tenon capsule (CRATER).
MATERIALS AND METHODS This randomized, prospective, interventional, comparative case series was conducted at the Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, www.corneajrnl.com |
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Chandigarh, India from April 2011 to September 2012. The study was performed in accordance with the tenets of the Declaration of Helsinki and was approved by and registered with the ethics committee of the Institute. Patients having primary pterygia and attending the Cornea Services were recruited for the study. Exclusion criteria included cases with recurrent pterygia and history of any ocular surgery or trauma, dry eye, and collagen vascular disease. Forty-nine eyes of 47 patients were randomized into 2 groups using a computer-generated random number table: group 1 included patients for free CAG and group 2 included patients for CLAG. After randomization, patients were informed about the type of procedure to be performed on them and were included only if they gave their consent. There were no dropouts between randomization and treatment. A detailed history was noted from the patients, followed by basic standard ophthalmologic examination, including uncorrected visual acuity, best corrected visual acuity, slitlamp biomicroscopy, Schirmer test, intraocular pressure by Goldmann applanation tonometry, keratometry, and slit-lamp photography, for documentation. Pterygium was evaluated in detail for each patient and dimensions were measured on the cornea (distance from limbus to apex of pterygium) and limbus (vertical distance between the superior and inferior edges of pterygium at the limbus) using a fine slit of the slit lamp. Pterygia were graded according to the classification given by Tan et al9: grade 1 (atrophic): episcleral vessels under the body of pterygium not obscured and clearly distinguished; grade 3 (fleshy): episcleral vessels totally obscured by the body of pterygium; grade 2 (intermediate): all other pterygia not falling into these 2 grades.
Cornea Volume 34, Number 2, February 2015
FIGURE 1. A, Line diagram showing nasal pterygium. B, Surgical technique of pterygium excision—extensive removal of Tenon layer up to the caruncle and 5 mm beyond the superior and inferior edge of pterygium, combined with limited resection of overlying conjunctiva.
All surgical procedures were performed by a single surgeon (A.K.J.). Surgery was performed under peribulbar anesthesia using a combination of 2% xylocaine and 0.5% bupivacaine. After standard ophthalmologic sterile preparation and draping, a lid speculum was used to expose the surgical field of the involved eye. Two 8-0 vicryl traction sutures were placed in the superior and inferior episcleral–limbal area to improve exposure. The size of pterygium was measured using calipers. A combination of dissection (both blunt and sharp) and stripping was carried out to separate the head of pterygium from the underlying corneal tissue with the aim of releasing the traction on the nasal conjunctiva. The medial rectus was then identified and isolated using a muscle hook to avoid damage to the muscle and its sheath during dissection. An extended removal of pathological pterygium tissue (ie, subconjunctival fibrovascular tissue and Tenon capsule) was then carried out up to the caruncle (Fig. 1). The Tenon layer was also excised underneath the inferior and superior conjunctival free edge for approximately 5 mm. After ensuring hemostasis, limited resection of conjunctiva was performed from the tip of the released pterygium head up to the limbus. This usually amounted to approximately 3 to 4 mm of conjunctiva being resected. The conjunctiva was then allowed to retract over the bare sclera and the area was measured with calipers both horizontally and vertically at midpoints of the 2 meridians. The
conjunctival graft was dissected from the superotemporal bulbar conjunctiva. The intended graft area (taken equal to the size of bare sclera, to avoid overriding of the graft edges by the native conjunctiva and consequent development of implantation cysts) was marked in the superotemporal zone with a gentian violet marker pen. Subconjunctival injection of 2% lidocaine with adrenaline (1:100,000) was given to balloon the conjunctiva, creating a plane for dissection between the conjunctiva and Tenon capsule. Care was taken to dissect as thin a conjunctival flap as possible without inclusion of Tenon tissue to avoid retraction of the graft in the postoperative period. Dissection was carried out using blunt-tipped Vannas scissors and nontoothed conjunctival forceps from the fornix to approximately 1.5 mm from the limbus in group 1 (CAG) (Fig. 2), whereas in group 2 (CLAG), the graft was harvested in a similar manner but dissection was carried out to include up to 0.5 mm of limbal tissue in the graft to ensure inclusion of conjunctiva containing rete pegs along with Palisades of Vogt (Fig. 2). In both groups, the free graft was placed on the clear cornea with the undersurface facing up. A commercially available fibrin adhesive (Tisseel VH Fibrin sealant; Baxter AG, Vienna, Austria) was used for apposition of the free graft to the bare sclera. In brief, a drop of fibrinogen solution was first placed on the bare sclera and spread out with a cannula needle. The thrombin component was then applied on the undersurface of the graft placed on top of the cornea. The graft coated with thrombin solution was then immediately flipped over and spread out onto the bare sclera coated with fibrinogen solution using 2 McPherson forceps. Care was taken to ensure that the limbal side of the harvested graft was oriented toward the limbus at the site of transplantation. The graft was recessed back from the limbus for approximately 0.5 to 1 mm and the sides of the graft were closely opposed to the edges of the
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Surgical Technique
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CRATER Technique for CAG and CLAG
FIGURE 2. A, Grade 2 nasal pterygium. B, Donor site of CLAG. Note the incorporation of limbal tissue into the excised area. C, Appearance of same eye (as shown in A and B) after 6 weeks of surgery. D, Grade 3 nasal pterygium extending up to the pupillary area. E, Intraoperative fluorescein staining of the same eye area of excised CAG leaving a 2-mm strip of intact conjunctiva at the limbus, which is not taking up the dye (white arrow) and area of excised pterygium nasally (red arrow). F, Same eye as in (C) and (D) after 6 weeks of surgery.
recipient conjunctiva. After 5 minutes, the excess of fibrin glue from the margins of the graft was excised with Vannas scissors. Patients received subconjunctival injection of gentamicin 20 mg/0.5 mL and dexamethasone 2 mg/0.5 mL in the inferior bulbar conjunctiva away from the graft site. After instillation of antibiotic drops (0.5% moxifloxacin), the eye was patched for 24 hours. An antibiotic–steroid combination of tobramycin and dexamethasone 4 times a day was prescribed in the initial postoperative period and tapered over a period of 4 weeks. Lubricant eye drops containing 1% carboxymethyl cellulose were also prescribed 4 times a day for 6 weeks.
Evaluation of Results All patients were scheduled for follow-up visits on days 1, 3, 7, 14 and 21 and at 6 weeks, 3, 6, 9, and 12 months after surgery. To ensure compliance, patients were reminded of their visits through telephone 1 day before their scheduled follow-up. All postoperative observations were made by a single surgeon (A.K.J.) to ensure uniformity. Graft stability23 and time to complete epithelialization of the donor site and graft were noted in the first few visits. Special attention was paid to healing of the donor site to detect any complications, and recurrence of the pterygium was looked for at every visit. True corneal pterygium recurrence was defined as any growth of fibrovascular tissue across the limbus. Recurrence was graded on a scale of 1 to 4 as described by Prabhasawat et al.24 Briefly, recurrence was graded as follows: grade 1, normal appearance of the operated site; grade 2, presence of fine episcleral vessels in the excised area, extending to the limbus, but without any fibrous tissue; grade 3, presence of fibrovascular tissue in the excised area, reaching the limbus, but not invading the cornea; and grade 4, true corneal recurrence, with fibrovascular tissue invading the cornea. For the purpose of this study, a satisfactory cosmetic outcome was taken as described previously,25 that is, absence of any of the following features in the area of pterygium removal on external examination: gathering/folds of conjunctival tissue at the site of autograft, conjunctival injection, new blood vessel growth, or scarring. Copyright Ó 2014 Wolters Kluwer Health, Inc. All rights reserved.
Statistical Analysis Statistical analysis was carried out using Statistical Package for Social Sciences (version 16.0; SPSS Inc, Chicago, IL). Significance was set at P , 0.05. Data were compared using parametric or nonparametric tests based on normality.
RESULTS Forty-nine pterygium surgeries were performed for primary nasal pterygium in 47 patients. Two patients underwent bilateral surgery. Twenty-four patients (51%) were men and 23 (49%) were women. The mean follow-up period was 63 weeks (range, 54–81 weeks). All patients (47 patients, 49 surgical procedures) completed the minimum duration of 1-year followup and were consequently included in data analysis. Mean size of the pterygium on the cornea (3.1 6 1.2 mm in CAG group and 3.4 6 3.4 mm in the CLAG group) was comparable. Mean width of pterygium at the limbus (5.1 6 1.2 mm in CAG group and 5.3 6 1.1 mm in the CLAG group) was also similar. Other patient characteristics for both groups are given in Table 1. No statistically significant differences existed between the 2 groups in preoperative characteristics. Being primary cases, all pterygia could be easily dissected off the cornea using a combination of blunt and sharp dissection and avulsion. No significant corneal scarring
TABLE 1. Comparison of Patient Characteristics and Preoperative Parameters Between the 2 Groups
Mean age, yr Total number of eyes Right eye:left eye Grade II pterygium Grade III pterygium Mean size of pterygium on cornea, mm Mean size of pterygium on limbus, mm Preoperative average keratometry reading, diopters
Group 1 (CAG)
Group 2 (CLAG)
48.8 6 14.1 24 11:13 8 eyes 16 eyes 3.1 6 1.2 5.1 6 1.2 42.9 6 1.8
39.6 6 10.8 25 11:14 5 eyes 20 eyes 3.4 6 3.4 5.3 6 1.1 42.9 6 1.7
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or adhesions were noted in any patient intraoperatively. On the first postoperative day, the size of the epithelial defect at the recipient and donor sites was comparable between the 2 groups (Table 2). The epithelial defect at the recipient site extended from the cornea to the area between the graft and host tissue in all cases. A few cases had irregular variegated epithelial defect on the surface of the graft, which may have occurred either due to inadvertent instrument touch or desiccation of the graft while being harvested and consequent damage to the superficial epithelium. This epithelial defect persisted beyond 1 week in 3 eyes (12.5%) in the CAG and none in the CLAG group. By the end of 2 weeks, there was no epithelial defect at the recipient site in both groups. The epithelial defect on the donor site persisted beyond 1 week in 2 eyes in each group, which also healed by the end of 2 weeks. Graft edema was present in 2 eyes (1 in each group) at day 1 postoperatively and in 6 eyes [4 eyes in CAG (16.7%) and 2 eyes (8%) in CLAG group] on the third postoperative day. Graft edema resolved in all eyes by the end of 2 weeks postoperatively. A subconjunctival cyst was detected in 1 eye (CLAG group) at 3 weeks postoperatively. Dellen formation occurred in 1 eye (CAG group). None of the patients developed diplopia or decrease in visual acuity (uncorrected visual acuity or best corrected visual acuity). The difference in complications in both groups was not statistically significant. No recurrence of any grade (either corneal or conjunctival) was detected in any eye in both groups during the followup period and at the end of 12 months. None of the patients had any gathering/folds of conjunctival tissue at the site of autograft, conjunctival injection, or new blood vessel growth at the site of excision. A faint scar at the posterior (caruncular) edge of the graft was, however, noticed in most patients. One patient in the CAG group and 2 patients in the CLAG group also showed evidence of corneal scarring at the operated site when examined at the slit lamp, which, however, was not obvious on external examination. No sign suggestive of localized limbal stem cell deficiency (eg, pannus or pseudopterygium formation) was noted in any patient in the CLAG group during the follow-up period.
DISCUSSION In 1985, Kenyon et al4 described CAG for treatment of pterygium with low a recurrence rate of 5.3% and the procedure became very popular. However, later studies
TABLE 2. Comparison of Postoperative Parameters in 2 Groups
Graft size Size of epithelial defect at the recipient site on first postoperative day Size of epithelial defect at the donor site on first postoperative day
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Group 1 (CAG), mm2
Group 2 (CLAG) mm2
P
47.8 6 16.2 31.5 6 28.6
48.1 6 18.8 32.4 6 15.4
0.51 0.9
32.7 6 12.3
36.0 6 16.5
0.43
showed varying recurrence rates with free conjunctival autografting ranging from 2% to 39%.9,13–17 Even with the inclusion of limbal stem cells, recurrence rates of 0% to –18% were reported.7,18–20 An important factor emphasized in reducing recurrences after pterygium excision has been the removal of the Tenon layer.26 This may be explained by studies performed by Denk et al27,28 and Kria et al29,30 on the Tenon layer and in vitro modulation of pterygial fibroblasts by growth factors, which demonstrated that fibroblasts in the Tenon layer may be stimulated to produce hyaluronate or cause scarring after glaucoma procedures. The same mechanism may also hold true for pterygium excision. This prospective randomized study performed for primary pterygia using the CRATER technique showed 0% recurrence rates for both CLAG and CAG. In our series, subconjunctival fibrovascular pterygium tissue and Tenon capsule were excised extensively up to the caruncle under the body of the pterygium. The Tenon capsule was also excised for 5 mm beyond the superonasal and inferonasal edge of the pterygium folds. However, the overlying conjunctiva was preserved as far as possible with only as much being sacrificed as was absolutely necessary to ensure good apposition between the graft and recipient bed edges. The rationale of using this technique was 2-fold: a smaller raw area created at the pterygium site (by preserving the native nasal conjunctiva) and donor site (due to the smaller graft consequently required) would heal quickly and preserve more untouched conjunctiva superiorly for any future glaucoma filtering surgeries; simultaneous extensive dissection of the underlying Tenon layer could be expected to reduce recurrence rates and scarring. Mejía et al31 in their retrospective series of outcomes of primary pterygium surgery using CAG for 88 eyes and CLAG for 24 eyes reported a recurrence rate of 1.1% (1 of 88 eyes) in the CAG group and 4.1% (1 of 24 eyes) in the CLAG group. Although the authors did not compare the recurrence rates between the 2 groups, it seems unlikely that the difference will reach statistical significance, and hence both procedures seem to be equally effective for primary pterygia. A few studies have also directly compared the outcomes in terms of recurrence for CAG versus CLAG in primary and/or recurrent pterygia. Al Fayez18 in his series of 79 patients with advanced primary or recurrent pterygia reported no recurrence in 43 patients who underwent CLAG (28 with primary pterygia and 15 with recurrent pterygia) with a minimum of 3 years of follow-up. In patients who underwent CAG, a recurrence rate of 33.3% in patients with recurrent pterygia (4 of 12 eyes) and 8.3% in patients with primary pterygia was reported (2of 24 eyes). The higher recurrence rate seen with CAG compared with CLAG was significant only for recurrent pterygia (P = 0.028), and not for primary pterygia (P = 0.208). The authors thus concluded that both techniques were equally effective in cases of advanced primary pterygia, whereas limbal transplantation seemed to be more effective than free conjunctival transplantation for treatment of recurrent pterygia. Al Fayez22 while comparing CAG and CLAG for recurrent pterygia over a mean follow-up of 62 months, reported a 10% recurrence rate (10 of 100 eyes) for the CAG Copyright Ó 2014 Wolters Kluwer Health, Inc. All rights reserved.
Cornea Volume 34, Number 2, February 2015
group and a 1% recurrence rate (1 of 105 eyes) for CLAG group, with CLAG being significantly more efficacious (P = 0.004) in this cohort of recurrent pterygia. Kheirkhah et al21 reported on the outcomes of a prospectively performed randomized controlled trial comparing CLAG with CAG in primary and recurrent pterygia, where both surgical techniques were augmented with the application of intraoperative mitomycin C 0.02% for 3 minutes. Of the 78 operated eyes that achieved a minimal follow-up of 12 months, there was a 0% recurrence rate in CLAG group (33 primary and 6 recurrent pterygia), whereas a 5.1% recurrence rate was seen in the CAG group (2of 39 eyes), including 1 of 31 patients (3.2%) with primary pterygia and 1 of 8 patients (12.5%) with recurrent pterygia. The recurrence rate was not significant between the 2 groups, that is, between CAG and CLAG (P = 0.15) or between primary (P = 0.30) and recurrent (P = 0.37) groups, demonstrating that both procedures were equally effective, more so for primary pterygia. The prime concern in including limbal tissue in the autograft is the risk of inducing limbal stem cell deficiency at the donor site. Previous reports have documented focal limbal stem cell deficiency by impression cytology in patients after surgeries involving the limbus.32,33 Al Fayez22 did not report evidence of limbal damage at the donor site in any of the operated eyes and attributed it to meticulous surgical technique, including among others use of a sharp blade/ diamond knife to avoid the crushing effect of scissors on the delicate limbal tissue, planar dissection, and avoiding unnecessary damage to the Bowman layer. No limbal damage was seen in any case in our series also. However, Kheirkhah et al21 in their series noted development of localized pannus at the donor site in 5 of 39 eyes (12.8%) that underwent CLAG. Of these 5 eyes, 1 developed pseudopterygium at the donor site. This pannus possibly represents a clinical manifestation of limbal stem cell population damage/depletion at the site where limbal tissue is harvested. The potential for inducing limbal damage thus does represent a real risk in CLAG. This combined with the fact that CLAG is more time consuming and requires greater surgical expertise than CAG, may make CAG with the CRATER technique a better alternative for treatment of primary pterygia. The authors would like to acknowledge a few limitations of the study. The sample size was relatively small compared with earlier studies. Also, the mean follow-up period of 64 weeks was shorter compared with other studies, but all patients completed at least 1 year of follow-up and had no evidence of either conjunctival or corneal recurrence. As up to 90% of recurrences are reported to occur within this period18,34 and rarely after 3 years, it is unlikely that any recurrence was missed. The source of the epithelium covering the scleral defect at the site of pterygium excision (ie, where the graft was recessed from the limbus) was not determined precisely in all cases. However, in a few cases of CLAG, the observer (A.K.J.) noted pigmentation at the limbal edge of the graft spreading toward the cornea, implying that the defect was being covered by proliferation from the limbal epithelium of the graft. Although the study is underpowered to determine the difference between these 2 techniques, we found a low recurrence rate for both CAG and CLAG in fibrin glue– Copyright Ó 2014 Wolters Kluwer Health, Inc. All rights reserved.
CRATER Technique for CAG and CLAG
assisted primary pterygium surgery using the CRATER technique of limited conjunctival resection combined with extensive removal of the underlying Tenon capsule. Larger studies may be able to better clarify the role of incorporation of limbal tissue in CAG in cases of primary pterygia. REFERENCES 1. Hilgers JH. Pterygium: its incidence, heredity and etiology. Am J Ophthalmol. 1960;50:635–644. 2. Durkin SR, Abhary S, Newland HS, et al. The prevalence, severity and risk factors for pterygium in central Myanmar: the Meiktila Eye Study. Br J Ophthalmol. 2008;92:25–29. 3. Hirst LW. The treatment of pterygium. Surv Ophthalmol. 2003;48:145–180. 4. Kenyon KR, Wagoner MD, Hettinger ME. Conjunctival autograft transplantation for advanced and recurrent pterygium. Ophthalmology. 1985;92:1461–1470. 5. Serrano F. Plastia conjuntival libre en la cirugÍa del pterigion. Arch Soc Am Oftal Optom. 1977;12:97–102. 6. Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989;96:709–722; discussion 722–723. 7. Shimazaki J, Yang HY, Tsubota K. Limbal autograft transplantation for recurrent and advanced pterygia. Ophthalmic Surg Lasers. 1996;27:917–923. 8. Sánchez-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;82:661–665. 9. Tan DT, Chee SP, Dear KB, et al. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision. Arch Ophthalmol. 1997;115:1235–1240. 10. Dushku N, Reid TW. Immunohistochemical evidence that human pterygia originate from an invasion of vimentin-expressing altered limbal epithelial basal cells. Curr Eye Res. 1994;13:473–481. 11. Tseng SC. Concept and application of limbal stem cells. Eye (Lond). 1989;3(pt 2):141–157. 12. Tseng SC, Chen JJY, Huang AJW, et al. Classification of conjunctival surgeries for corneal diseases based on stem cell concept. Ophthalmol Clin North Am. 1990;3:595–610. 13. Lewallen S. A randomized trial of conjunctival autografting for pterygium in the tropics. Ophthalmology. 1989;96:1612–1614. 14. Rao SK, Lekha T, Sitalakshmi G, et al. Conjunctival autograft for pterygium surgery: how well does it prevent recurrence? Ophthalmic Surg Lasers. 1997;28:875–877. 15. 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;120:151–160. 16. Luanratanakorn P, Ratanapakorn T, Suwan-Apichon O, et al. Randomised controlled study of conjunctival autograft versus amniotic membrane graft in pterygium excision. Br J Ophthalmol. 2006;90: 1476–1480. 17. Karabatsas CH, Marsh GW, Cook AM, et al. Different therapeutic approaches and outcome in the treatment of pterygium. Eur J Ophthalmol. 1998;8:148–152. 18. Al Fayez MF. Limbal versus conjunctival autograft transplantation for advanced and recurrent pterygium. Ophthalmology. 2002;109: 1752–1755. 19. Mutlu FM, Sobaci G, Tatar T, et al. A comparative study of recurrent pterygium surgery: limbal conjunctival autograft transplantation versus mitomycin C with conjunctival flap. Ophthalmology. 1999;106:817–821. 20. Rao SK, Lekha T, Mukesh BN, et al. Conjunctival-limbal autografts for primary and recurrent pterygia: technique and results. Indian J Ophthalmol. 1998;46:203–209. 21. Kheirkhah A, Hashemi H, Adelpour M, et al. Randomized trial of pterygium surgery with mitomycin C application using conjunctival autograft versus conjunctival-limbal autograft. Ophthalmology. 2012; 119:227–232. 22. Al Fayez MF. Limbal-conjunctival vs conjunctival autograft transplant for recurrent pterygia—a prospective randomized controlled trial. JAMA Ophthalmol. 2013;131:11–16.
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23. Srinivasan S, Dollin M, McAllum P, et al. Fibrin glue versus sutures for attaching the conjunctival autograft in pterygium surgery: a prospective observer masked clinical trial. Br J Ophthalmol. 2009;93:215–218. 24. Prabhasawat P, Barton K, Burkett G, et al. Comparison of conjunctival autografts, amniotic membrane grafts and primary closure for pterygium excision. Ophthalmology. 1997;104:974–985. 25. Hirst LW. Recurrent pterygium surgery using pterygium extended removal followed by extended conjunctival transplant: recurrence rate and Cosmesis. Ophthalmology. 2009;116:1278–1286. 26. Barraquer JI. Etiology, pathogenesis, and treatment of the pterygium. Trans New Orleans Acad Ophthalmol. 1980;28:167–178. 27. Denk PO, Hoppe J, Hoppe V, et al. Effect of growth factors on the activation of human Tenon’s capsule fibroblasts. Curr Eye Res. 2003; 27:35–44. 28. Denk PO, Roth-Eichhorn S, Gressner AM, et al. Cytokine regulation of hyaluronate production by human Tenon’s capsule fibroblasts. Curr Eye Res. 2000;20:77–80.
29. Kria L, Ohira A, Amemiya T. Growth factors in cultured pterygium fibroblasts: immunohistochemical and ELISA analysis. Graefes Arch Clin Exp Ophthalmol. 1998;236:702–708. 30. Kria L, Ohira A, Amemiya T. TNP-470 (a fungus-derived inhibitor of angiogenesis) reduces proliferation of cultured fibroblasts isolated from primary pterygia: a possible drug therapy for pterygia. Curr Eye Res. 1998;17:986–993. 31. Mejía LF, Sánchez JG, Escobar H. Management of primary pterygia using free conjunctival and limbal-conjunctival autografts without antimetabolites. Cornea. 2005;24:972–975. 32. Sridhar MS, Vemuganti GK, Bansal AK, et al. Impression cytologyproven corneal stem cell deficiency in patients after surgeries involving the limbus. Cornea. 2001;20:145–148. 33. Gris O, Güell JL, del Campo Z. Limbal-conjunctival autograft transplantation for the treatment of recurrent pterygium. Ophthalmology. 2000;107:270–273. 34. Hirst LW, Sebban A, Chant D. Pterygium recurrence time. Ophthalmology. 1994;101:755–758.
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Outcomes of Fibrin Glue-Assisted Conjunctival Versus Conjunctivolimbal Autograft in Primary Pterygia With a New Technique of Conjunctival Resection and Tenon Extended Removal Chintan Malhotra, MS, Arun K. Jain, MD, Ashish Sawhney, MS, Nishant Nawani, MS, and Jagat Ram, MS
Purpose: The aim of this study was to compare the recurrence rates
for primary pterygia after fibrin glue–assisted conjunctival autograft (CAG) versus conjunctivolimbal autograft (CLAG) transplantation, using a technique of limited conjunctival resection and Tenon extended removal.
Method: In this comparative case series, 49 eyes of 47 patients with primary nasal pterygium were included. Patients were randomized into 2 groups to undergo fibrin glue–assisted CAG (group 1, 24 eyes) or fibrin glue–assisted CLAG (group 2, 25 eyes) following excision of pterygium. The surgical technique used in all patients involved limited conjunctival resection combined with extensive removal of the Tenon capsule up to the caruncle medially and also 5 mm beyond the inferior and superior free edges of the conjunctiva. The main outcome measure studied was the absence or presence of recurrence. Results: There was 0% recurrence rate in both groups after a mean follow-up of 63 weeks (range, 54–81 weeks) with all eyes completing at least 1-year of follow-up. Conclusions: Fibrin glue–assisted CAG and CLAG using the technique of conjunctival resection and Tenon extended removal were equally efficacious in terms of preventing recurrences in patients with primary pterygia in our series. Key Words: pterygium, conjunctival autograft, conjunctivolimbal autograft (Cornea 2015;34:193–198)
P
terygium is a common degenerative condition found most commonly in the “pterygium area,” defined by geographical boundaries of 40-degree latitudes north and south of the equator.1 In these areas, prevalence of up to 22% has been Received for publication June 22, 2014; revision received October 9, 2014; accepted October 13, 2014. Published online ahead of print December 3, 2014. From the Advanced Eye Centre, Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. The authors have no funding or conflicts of interest to disclose. Reprints: Arun K. Jain, MD, Advanced Eye Centre, Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Room No. 110, Chandigarh 160012, India (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
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reported,1,2 whereas elsewhere, reported prevalence rates usually do not exceed 2% of the general population. Indications for removal of pterygium include decreased vision that may be either due to proximity of pterygium to the visual axis or induced astigmatism, restriction of ocular movements, and cosmesis. Despite a wide variety of surgical techniques that have been described for its management ranging from simple resection or bare sclera technique to avulsion, removal and primary closure, pterygium head transplantation, concomitant beta radiation, conjunctival autograft (CAG), conjunctivolimbal autograft (CLAG), and use of amniotic membrane with/without conjunctival graft3–7 prevention of recurrences still remains a challenge. Recurrence rates varying from as low as 2% to up to 80% have been recorded, depending on the surgical technique used.3 Transplantation of CAG or CLAG has been reported to be the most effective method of lowering recurrence rates and occurrence of complications.8,9 The rationale for including limbal tissue was based on certain theories, which suggested that the healthy limbal epithelium acts as a junctional barrier to conjunctival migration onto the corneal surface.10,11 Also, pterygium has been speculated to represent “local limbal deficiency.”12 As a consequence, it has been assumed that inclusion of limbal epithelium in the conjunctival graft for pterygium surgery would achieve better anatomic and functional outcomes by restoring the barrier function of the limbus. Recurrence rates of 2% to 39% for CAG9,13–17 and 0% to 18% for CLAG7,18–20 have been reported by previous investigators. Previous studies directly comparing the 2 techniques have included patients with both primary and recurrent pterygia,18,21 or recurrent pterygia only,22 with mitomycin C also being used as an adjuvant by Kheirkhah et al.21 As no unanimity of opinion exists as to which technique is better, this study was designed to directly compare prospectively and report our experience with the outcomes of fibrin glue–assisted CAG and CLAG for primary pterygia, using a technique of limited conjunctival resection combined with extended removal of the Tenon capsule (CRATER).
MATERIALS AND METHODS This randomized, prospective, interventional, comparative case series was conducted at the Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, www.corneajrnl.com |
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Chandigarh, India from April 2011 to September 2012. The study was performed in accordance with the tenets of the Declaration of Helsinki and was approved by and registered with the ethics committee of the Institute. Patients having primary pterygia and attending the Cornea Services were recruited for the study. Exclusion criteria included cases with recurrent pterygia and history of any ocular surgery or trauma, dry eye, and collagen vascular disease. Forty-nine eyes of 47 patients were randomized into 2 groups using a computer-generated random number table: group 1 included patients for free CAG and group 2 included patients for CLAG. After randomization, patients were informed about the type of procedure to be performed on them and were included only if they gave their consent. There were no dropouts between randomization and treatment. A detailed history was noted from the patients, followed by basic standard ophthalmologic examination, including uncorrected visual acuity, best corrected visual acuity, slitlamp biomicroscopy, Schirmer test, intraocular pressure by Goldmann applanation tonometry, keratometry, and slit-lamp photography, for documentation. Pterygium was evaluated in detail for each patient and dimensions were measured on the cornea (distance from limbus to apex of pterygium) and limbus (vertical distance between the superior and inferior edges of pterygium at the limbus) using a fine slit of the slit lamp. Pterygia were graded according to the classification given by Tan et al9: grade 1 (atrophic): episcleral vessels under the body of pterygium not obscured and clearly distinguished; grade 3 (fleshy): episcleral vessels totally obscured by the body of pterygium; grade 2 (intermediate): all other pterygia not falling into these 2 grades.
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FIGURE 1. A, Line diagram showing nasal pterygium. B, Surgical technique of pterygium excision—extensive removal of Tenon layer up to the caruncle and 5 mm beyond the superior and inferior edge of pterygium, combined with limited resection of overlying conjunctiva.
All surgical procedures were performed by a single surgeon (A.K.J.). Surgery was performed under peribulbar anesthesia using a combination of 2% xylocaine and 0.5% bupivacaine. After standard ophthalmologic sterile preparation and draping, a lid speculum was used to expose the surgical field of the involved eye. Two 8-0 vicryl traction sutures were placed in the superior and inferior episcleral–limbal area to improve exposure. The size of pterygium was measured using calipers. A combination of dissection (both blunt and sharp) and stripping was carried out to separate the head of pterygium from the underlying corneal tissue with the aim of releasing the traction on the nasal conjunctiva. The medial rectus was then identified and isolated using a muscle hook to avoid damage to the muscle and its sheath during dissection. An extended removal of pathological pterygium tissue (ie, subconjunctival fibrovascular tissue and Tenon capsule) was then carried out up to the caruncle (Fig. 1). The Tenon layer was also excised underneath the inferior and superior conjunctival free edge for approximately 5 mm. After ensuring hemostasis, limited resection of conjunctiva was performed from the tip of the released pterygium head up to the limbus. This usually amounted to approximately 3 to 4 mm of conjunctiva being resected. The conjunctiva was then allowed to retract over the bare sclera and the area was measured with calipers both horizontally and vertically at midpoints of the 2 meridians. The
conjunctival graft was dissected from the superotemporal bulbar conjunctiva. The intended graft area (taken equal to the size of bare sclera, to avoid overriding of the graft edges by the native conjunctiva and consequent development of implantation cysts) was marked in the superotemporal zone with a gentian violet marker pen. Subconjunctival injection of 2% lidocaine with adrenaline (1:100,000) was given to balloon the conjunctiva, creating a plane for dissection between the conjunctiva and Tenon capsule. Care was taken to dissect as thin a conjunctival flap as possible without inclusion of Tenon tissue to avoid retraction of the graft in the postoperative period. Dissection was carried out using blunt-tipped Vannas scissors and nontoothed conjunctival forceps from the fornix to approximately 1.5 mm from the limbus in group 1 (CAG) (Fig. 2), whereas in group 2 (CLAG), the graft was harvested in a similar manner but dissection was carried out to include up to 0.5 mm of limbal tissue in the graft to ensure inclusion of conjunctiva containing rete pegs along with Palisades of Vogt (Fig. 2). In both groups, the free graft was placed on the clear cornea with the undersurface facing up. A commercially available fibrin adhesive (Tisseel VH Fibrin sealant; Baxter AG, Vienna, Austria) was used for apposition of the free graft to the bare sclera. In brief, a drop of fibrinogen solution was first placed on the bare sclera and spread out with a cannula needle. The thrombin component was then applied on the undersurface of the graft placed on top of the cornea. The graft coated with thrombin solution was then immediately flipped over and spread out onto the bare sclera coated with fibrinogen solution using 2 McPherson forceps. Care was taken to ensure that the limbal side of the harvested graft was oriented toward the limbus at the site of transplantation. The graft was recessed back from the limbus for approximately 0.5 to 1 mm and the sides of the graft were closely opposed to the edges of the
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Surgical Technique
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CRATER Technique for CAG and CLAG
FIGURE 2. A, Grade 2 nasal pterygium. B, Donor site of CLAG. Note the incorporation of limbal tissue into the excised area. C, Appearance of same eye (as shown in A and B) after 6 weeks of surgery. D, Grade 3 nasal pterygium extending up to the pupillary area. E, Intraoperative fluorescein staining of the same eye area of excised CAG leaving a 2-mm strip of intact conjunctiva at the limbus, which is not taking up the dye (white arrow) and area of excised pterygium nasally (red arrow). F, Same eye as in (C) and (D) after 6 weeks of surgery.
recipient conjunctiva. After 5 minutes, the excess of fibrin glue from the margins of the graft was excised with Vannas scissors. Patients received subconjunctival injection of gentamicin 20 mg/0.5 mL and dexamethasone 2 mg/0.5 mL in the inferior bulbar conjunctiva away from the graft site. After instillation of antibiotic drops (0.5% moxifloxacin), the eye was patched for 24 hours. An antibiotic–steroid combination of tobramycin and dexamethasone 4 times a day was prescribed in the initial postoperative period and tapered over a period of 4 weeks. Lubricant eye drops containing 1% carboxymethyl cellulose were also prescribed 4 times a day for 6 weeks.
Evaluation of Results All patients were scheduled for follow-up visits on days 1, 3, 7, 14 and 21 and at 6 weeks, 3, 6, 9, and 12 months after surgery. To ensure compliance, patients were reminded of their visits through telephone 1 day before their scheduled follow-up. All postoperative observations were made by a single surgeon (A.K.J.) to ensure uniformity. Graft stability23 and time to complete epithelialization of the donor site and graft were noted in the first few visits. Special attention was paid to healing of the donor site to detect any complications, and recurrence of the pterygium was looked for at every visit. True corneal pterygium recurrence was defined as any growth of fibrovascular tissue across the limbus. Recurrence was graded on a scale of 1 to 4 as described by Prabhasawat et al.24 Briefly, recurrence was graded as follows: grade 1, normal appearance of the operated site; grade 2, presence of fine episcleral vessels in the excised area, extending to the limbus, but without any fibrous tissue; grade 3, presence of fibrovascular tissue in the excised area, reaching the limbus, but not invading the cornea; and grade 4, true corneal recurrence, with fibrovascular tissue invading the cornea. For the purpose of this study, a satisfactory cosmetic outcome was taken as described previously,25 that is, absence of any of the following features in the area of pterygium removal on external examination: gathering/folds of conjunctival tissue at the site of autograft, conjunctival injection, new blood vessel growth, or scarring. Copyright Ó 2014 Wolters Kluwer Health, Inc. All rights reserved.
Statistical Analysis Statistical analysis was carried out using Statistical Package for Social Sciences (version 16.0; SPSS Inc, Chicago, IL). Significance was set at P , 0.05. Data were compared using parametric or nonparametric tests based on normality.
RESULTS Forty-nine pterygium surgeries were performed for primary nasal pterygium in 47 patients. Two patients underwent bilateral surgery. Twenty-four patients (51%) were men and 23 (49%) were women. The mean follow-up period was 63 weeks (range, 54–81 weeks). All patients (47 patients, 49 surgical procedures) completed the minimum duration of 1-year followup and were consequently included in data analysis. Mean size of the pterygium on the cornea (3.1 6 1.2 mm in CAG group and 3.4 6 3.4 mm in the CLAG group) was comparable. Mean width of pterygium at the limbus (5.1 6 1.2 mm in CAG group and 5.3 6 1.1 mm in the CLAG group) was also similar. Other patient characteristics for both groups are given in Table 1. No statistically significant differences existed between the 2 groups in preoperative characteristics. Being primary cases, all pterygia could be easily dissected off the cornea using a combination of blunt and sharp dissection and avulsion. No significant corneal scarring
TABLE 1. Comparison of Patient Characteristics and Preoperative Parameters Between the 2 Groups
Mean age, yr Total number of eyes Right eye:left eye Grade II pterygium Grade III pterygium Mean size of pterygium on cornea, mm Mean size of pterygium on limbus, mm Preoperative average keratometry reading, diopters
Group 1 (CAG)
Group 2 (CLAG)
48.8 6 14.1 24 11:13 8 eyes 16 eyes 3.1 6 1.2 5.1 6 1.2 42.9 6 1.8
39.6 6 10.8 25 11:14 5 eyes 20 eyes 3.4 6 3.4 5.3 6 1.1 42.9 6 1.7
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or adhesions were noted in any patient intraoperatively. On the first postoperative day, the size of the epithelial defect at the recipient and donor sites was comparable between the 2 groups (Table 2). The epithelial defect at the recipient site extended from the cornea to the area between the graft and host tissue in all cases. A few cases had irregular variegated epithelial defect on the surface of the graft, which may have occurred either due to inadvertent instrument touch or desiccation of the graft while being harvested and consequent damage to the superficial epithelium. This epithelial defect persisted beyond 1 week in 3 eyes (12.5%) in the CAG and none in the CLAG group. By the end of 2 weeks, there was no epithelial defect at the recipient site in both groups. The epithelial defect on the donor site persisted beyond 1 week in 2 eyes in each group, which also healed by the end of 2 weeks. Graft edema was present in 2 eyes (1 in each group) at day 1 postoperatively and in 6 eyes [4 eyes in CAG (16.7%) and 2 eyes (8%) in CLAG group] on the third postoperative day. Graft edema resolved in all eyes by the end of 2 weeks postoperatively. A subconjunctival cyst was detected in 1 eye (CLAG group) at 3 weeks postoperatively. Dellen formation occurred in 1 eye (CAG group). None of the patients developed diplopia or decrease in visual acuity (uncorrected visual acuity or best corrected visual acuity). The difference in complications in both groups was not statistically significant. No recurrence of any grade (either corneal or conjunctival) was detected in any eye in both groups during the followup period and at the end of 12 months. None of the patients had any gathering/folds of conjunctival tissue at the site of autograft, conjunctival injection, or new blood vessel growth at the site of excision. A faint scar at the posterior (caruncular) edge of the graft was, however, noticed in most patients. One patient in the CAG group and 2 patients in the CLAG group also showed evidence of corneal scarring at the operated site when examined at the slit lamp, which, however, was not obvious on external examination. No sign suggestive of localized limbal stem cell deficiency (eg, pannus or pseudopterygium formation) was noted in any patient in the CLAG group during the follow-up period.
DISCUSSION In 1985, Kenyon et al4 described CAG for treatment of pterygium with low a recurrence rate of 5.3% and the procedure became very popular. However, later studies
TABLE 2. Comparison of Postoperative Parameters in 2 Groups
Graft size Size of epithelial defect at the recipient site on first postoperative day Size of epithelial defect at the donor site on first postoperative day
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Group 1 (CAG), mm2
Group 2 (CLAG) mm2
P
47.8 6 16.2 31.5 6 28.6
48.1 6 18.8 32.4 6 15.4
0.51 0.9
32.7 6 12.3
36.0 6 16.5
0.43
showed varying recurrence rates with free conjunctival autografting ranging from 2% to 39%.9,13–17 Even with the inclusion of limbal stem cells, recurrence rates of 0% to –18% were reported.7,18–20 An important factor emphasized in reducing recurrences after pterygium excision has been the removal of the Tenon layer.26 This may be explained by studies performed by Denk et al27,28 and Kria et al29,30 on the Tenon layer and in vitro modulation of pterygial fibroblasts by growth factors, which demonstrated that fibroblasts in the Tenon layer may be stimulated to produce hyaluronate or cause scarring after glaucoma procedures. The same mechanism may also hold true for pterygium excision. This prospective randomized study performed for primary pterygia using the CRATER technique showed 0% recurrence rates for both CLAG and CAG. In our series, subconjunctival fibrovascular pterygium tissue and Tenon capsule were excised extensively up to the caruncle under the body of the pterygium. The Tenon capsule was also excised for 5 mm beyond the superonasal and inferonasal edge of the pterygium folds. However, the overlying conjunctiva was preserved as far as possible with only as much being sacrificed as was absolutely necessary to ensure good apposition between the graft and recipient bed edges. The rationale of using this technique was 2-fold: a smaller raw area created at the pterygium site (by preserving the native nasal conjunctiva) and donor site (due to the smaller graft consequently required) would heal quickly and preserve more untouched conjunctiva superiorly for any future glaucoma filtering surgeries; simultaneous extensive dissection of the underlying Tenon layer could be expected to reduce recurrence rates and scarring. Mejía et al31 in their retrospective series of outcomes of primary pterygium surgery using CAG for 88 eyes and CLAG for 24 eyes reported a recurrence rate of 1.1% (1 of 88 eyes) in the CAG group and 4.1% (1 of 24 eyes) in the CLAG group. Although the authors did not compare the recurrence rates between the 2 groups, it seems unlikely that the difference will reach statistical significance, and hence both procedures seem to be equally effective for primary pterygia. A few studies have also directly compared the outcomes in terms of recurrence for CAG versus CLAG in primary and/or recurrent pterygia. Al Fayez18 in his series of 79 patients with advanced primary or recurrent pterygia reported no recurrence in 43 patients who underwent CLAG (28 with primary pterygia and 15 with recurrent pterygia) with a minimum of 3 years of follow-up. In patients who underwent CAG, a recurrence rate of 33.3% in patients with recurrent pterygia (4 of 12 eyes) and 8.3% in patients with primary pterygia was reported (2of 24 eyes). The higher recurrence rate seen with CAG compared with CLAG was significant only for recurrent pterygia (P = 0.028), and not for primary pterygia (P = 0.208). The authors thus concluded that both techniques were equally effective in cases of advanced primary pterygia, whereas limbal transplantation seemed to be more effective than free conjunctival transplantation for treatment of recurrent pterygia. Al Fayez22 while comparing CAG and CLAG for recurrent pterygia over a mean follow-up of 62 months, reported a 10% recurrence rate (10 of 100 eyes) for the CAG Copyright Ó 2014 Wolters Kluwer Health, Inc. All rights reserved.
Cornea Volume 34, Number 2, February 2015
group and a 1% recurrence rate (1 of 105 eyes) for CLAG group, with CLAG being significantly more efficacious (P = 0.004) in this cohort of recurrent pterygia. Kheirkhah et al21 reported on the outcomes of a prospectively performed randomized controlled trial comparing CLAG with CAG in primary and recurrent pterygia, where both surgical techniques were augmented with the application of intraoperative mitomycin C 0.02% for 3 minutes. Of the 78 operated eyes that achieved a minimal follow-up of 12 months, there was a 0% recurrence rate in CLAG group (33 primary and 6 recurrent pterygia), whereas a 5.1% recurrence rate was seen in the CAG group (2of 39 eyes), including 1 of 31 patients (3.2%) with primary pterygia and 1 of 8 patients (12.5%) with recurrent pterygia. The recurrence rate was not significant between the 2 groups, that is, between CAG and CLAG (P = 0.15) or between primary (P = 0.30) and recurrent (P = 0.37) groups, demonstrating that both procedures were equally effective, more so for primary pterygia. The prime concern in including limbal tissue in the autograft is the risk of inducing limbal stem cell deficiency at the donor site. Previous reports have documented focal limbal stem cell deficiency by impression cytology in patients after surgeries involving the limbus.32,33 Al Fayez22 did not report evidence of limbal damage at the donor site in any of the operated eyes and attributed it to meticulous surgical technique, including among others use of a sharp blade/ diamond knife to avoid the crushing effect of scissors on the delicate limbal tissue, planar dissection, and avoiding unnecessary damage to the Bowman layer. No limbal damage was seen in any case in our series also. However, Kheirkhah et al21 in their series noted development of localized pannus at the donor site in 5 of 39 eyes (12.8%) that underwent CLAG. Of these 5 eyes, 1 developed pseudopterygium at the donor site. This pannus possibly represents a clinical manifestation of limbal stem cell population damage/depletion at the site where limbal tissue is harvested. The potential for inducing limbal damage thus does represent a real risk in CLAG. This combined with the fact that CLAG is more time consuming and requires greater surgical expertise than CAG, may make CAG with the CRATER technique a better alternative for treatment of primary pterygia. The authors would like to acknowledge a few limitations of the study. The sample size was relatively small compared with earlier studies. Also, the mean follow-up period of 64 weeks was shorter compared with other studies, but all patients completed at least 1 year of follow-up and had no evidence of either conjunctival or corneal recurrence. As up to 90% of recurrences are reported to occur within this period18,34 and rarely after 3 years, it is unlikely that any recurrence was missed. The source of the epithelium covering the scleral defect at the site of pterygium excision (ie, where the graft was recessed from the limbus) was not determined precisely in all cases. However, in a few cases of CLAG, the observer (A.K.J.) noted pigmentation at the limbal edge of the graft spreading toward the cornea, implying that the defect was being covered by proliferation from the limbal epithelium of the graft. Although the study is underpowered to determine the difference between these 2 techniques, we found a low recurrence rate for both CAG and CLAG in fibrin glue– Copyright Ó 2014 Wolters Kluwer Health, Inc. All rights reserved.
CRATER Technique for CAG and CLAG
assisted primary pterygium surgery using the CRATER technique of limited conjunctival resection combined with extensive removal of the underlying Tenon capsule. Larger studies may be able to better clarify the role of incorporation of limbal tissue in CAG in cases of primary pterygia. REFERENCES 1. Hilgers JH. Pterygium: its incidence, heredity and etiology. Am J Ophthalmol. 1960;50:635–644. 2. Durkin SR, Abhary S, Newland HS, et al. The prevalence, severity and risk factors for pterygium in central Myanmar: the Meiktila Eye Study. Br J Ophthalmol. 2008;92:25–29. 3. Hirst LW. The treatment of pterygium. Surv Ophthalmol. 2003;48:145–180. 4. Kenyon KR, Wagoner MD, Hettinger ME. Conjunctival autograft transplantation for advanced and recurrent pterygium. Ophthalmology. 1985;92:1461–1470. 5. Serrano F. Plastia conjuntival libre en la cirugÍa del pterigion. Arch Soc Am Oftal Optom. 1977;12:97–102. 6. Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989;96:709–722; discussion 722–723. 7. Shimazaki J, Yang HY, Tsubota K. Limbal autograft transplantation for recurrent and advanced pterygia. Ophthalmic Surg Lasers. 1996;27:917–923. 8. Sánchez-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;82:661–665. 9. Tan DT, Chee SP, Dear KB, et al. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision. Arch Ophthalmol. 1997;115:1235–1240. 10. Dushku N, Reid TW. Immunohistochemical evidence that human pterygia originate from an invasion of vimentin-expressing altered limbal epithelial basal cells. Curr Eye Res. 1994;13:473–481. 11. Tseng SC. Concept and application of limbal stem cells. Eye (Lond). 1989;3(pt 2):141–157. 12. Tseng SC, Chen JJY, Huang AJW, et al. Classification of conjunctival surgeries for corneal diseases based on stem cell concept. Ophthalmol Clin North Am. 1990;3:595–610. 13. Lewallen S. A randomized trial of conjunctival autografting for pterygium in the tropics. Ophthalmology. 1989;96:1612–1614. 14. Rao SK, Lekha T, Sitalakshmi G, et al. Conjunctival autograft for pterygium surgery: how well does it prevent recurrence? Ophthalmic Surg Lasers. 1997;28:875–877. 15. 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;120:151–160. 16. Luanratanakorn P, Ratanapakorn T, Suwan-Apichon O, et al. Randomised controlled study of conjunctival autograft versus amniotic membrane graft in pterygium excision. Br J Ophthalmol. 2006;90: 1476–1480. 17. Karabatsas CH, Marsh GW, Cook AM, et al. Different therapeutic approaches and outcome in the treatment of pterygium. Eur J Ophthalmol. 1998;8:148–152. 18. Al Fayez MF. Limbal versus conjunctival autograft transplantation for advanced and recurrent pterygium. Ophthalmology. 2002;109: 1752–1755. 19. Mutlu FM, Sobaci G, Tatar T, et al. A comparative study of recurrent pterygium surgery: limbal conjunctival autograft transplantation versus mitomycin C with conjunctival flap. Ophthalmology. 1999;106:817–821. 20. Rao SK, Lekha T, Mukesh BN, et al. Conjunctival-limbal autografts for primary and recurrent pterygia: technique and results. Indian J Ophthalmol. 1998;46:203–209. 21. Kheirkhah A, Hashemi H, Adelpour M, et al. Randomized trial of pterygium surgery with mitomycin C application using conjunctival autograft versus conjunctival-limbal autograft. Ophthalmology. 2012; 119:227–232. 22. Al Fayez MF. Limbal-conjunctival vs conjunctival autograft transplant for recurrent pterygia—a prospective randomized controlled trial. JAMA Ophthalmol. 2013;131:11–16.
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23. Srinivasan S, Dollin M, McAllum P, et al. Fibrin glue versus sutures for attaching the conjunctival autograft in pterygium surgery: a prospective observer masked clinical trial. Br J Ophthalmol. 2009;93:215–218. 24. Prabhasawat P, Barton K, Burkett G, et al. Comparison of conjunctival autografts, amniotic membrane grafts and primary closure for pterygium excision. Ophthalmology. 1997;104:974–985. 25. Hirst LW. Recurrent pterygium surgery using pterygium extended removal followed by extended conjunctival transplant: recurrence rate and Cosmesis. Ophthalmology. 2009;116:1278–1286. 26. Barraquer JI. Etiology, pathogenesis, and treatment of the pterygium. Trans New Orleans Acad Ophthalmol. 1980;28:167–178. 27. Denk PO, Hoppe J, Hoppe V, et al. Effect of growth factors on the activation of human Tenon’s capsule fibroblasts. Curr Eye Res. 2003; 27:35–44. 28. Denk PO, Roth-Eichhorn S, Gressner AM, et al. Cytokine regulation of hyaluronate production by human Tenon’s capsule fibroblasts. Curr Eye Res. 2000;20:77–80.
29. Kria L, Ohira A, Amemiya T. Growth factors in cultured pterygium fibroblasts: immunohistochemical and ELISA analysis. Graefes Arch Clin Exp Ophthalmol. 1998;236:702–708. 30. Kria L, Ohira A, Amemiya T. TNP-470 (a fungus-derived inhibitor of angiogenesis) reduces proliferation of cultured fibroblasts isolated from primary pterygia: a possible drug therapy for pterygia. Curr Eye Res. 1998;17:986–993. 31. Mejía LF, Sánchez JG, Escobar H. Management of primary pterygia using free conjunctival and limbal-conjunctival autografts without antimetabolites. Cornea. 2005;24:972–975. 32. Sridhar MS, Vemuganti GK, Bansal AK, et al. Impression cytologyproven corneal stem cell deficiency in patients after surgeries involving the limbus. Cornea. 2001;20:145–148. 33. Gris O, Güell JL, del Campo Z. Limbal-conjunctival autograft transplantation for the treatment of recurrent pterygium. Ophthalmology. 2000;107:270–273. 34. Hirst LW, Sebban A, Chant D. Pterygium recurrence time. Ophthalmology. 1994;101:755–758.
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