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CLINICAL SCIENCE Role of Conjunctival Inflammation in Surgical Outcome After Amniotic Membrane Transplantation With or Without Fibrin Glue for Pterygium Ahmad Kheirkhah, MD, Victoria Casas, MD, Hosam Sheha, MD, Vadrevu K. Raju, MD, FRCS, and Scheffer C. G. Tseng, MD, PhD Purpose: To determine the clinical significance of postoperative Key Words: amniotic membrane, conjunctival inflammation, fibrin glue, mitomycin C, pterygium, suture conjunctival inflammation noted at the third or fourth week after intraoperative application of mitomycin C and amniotic membrane transplantation for pterygium. (Cornea 2008;27:56–63) Methods: This retrospective study included 27 eyes of 23 patients with primary (n = 12) or recurrent (n = 15) pterygia. All cases were operated by extensive removal of subconjunctival fibrovascular tissue and intraoperative application of 0.04% mitomycin C in the fornix, followed by amniotic membrane transplantation by using either fibrin glue (14 eyes) or sutures (13 eyes). Main outcome measures included development of conjunctival inflammation, pyogenic granuloma, and pterygium recurrence after surgery. Results: For a follow-up of 29.6 6 17.2 months (range, 6–56 months), 16 (59.3%) eyes without postoperative conjunctival inflammation resulted in favorable outcomes. Conjunctival inflammation around the surgical site was noted in the remaining 11 (40.7%) eyes and was significantly more common in eyes with sutures than those with fibrin glue (61.5% vs. 21.4%, respectively; P = 0.05). Among those with this inflammation, 7 eyes receiving subconjunctival injection of triamcinolone resulted in complete resolution and a good aesthetic outcome. Four eyes without this injection gradually developed conjunctival (n = 1) or corneal (n = 1) recurrence and/or pyogenic granuloma (n = 3). Conclusions: Host conjunctival inflammation is still common after intraoperative application of mitomycin C and amniotic membrane transplantation, especially when sutures are used in pterygium surgery. If left untreated, persistent inflammation may lead to a poor surgical outcome. Received for publication April 25, 2007; revision received July 20, 2007; accepted August 15, 2007. From the Ocular Surface Center, Miami, FL. Supported by an unrestricted grant from Ocular Surface Research and Education Foundation, Miami, FL. A.K. is a recipient of Joseph Swiger and Eye Foundation of America Fellowship from Ocular Surface Research and Education Foundation, Miami, FL. Dr. Tseng and his family are .5% shareholders of TissueTech, which owns US patents 6152142 and 6326019 on the method of preparation and clinical uses of human amniotic membrane distributed by Bio-Tissue. All other authors state that they have no proprietary interest in the products named in this article. Reprints: Scheffer C.G. Tseng, Ocular Surface Center, 7000 SW 97 Avenue, Suite 213, Miami, FL 33173 (e-mail: [email protected]). Copyright Ó 2007 by Lippincott Williams & Wilkins 56 P terygium is characterized by the encroachment of a fleshy fibrovascular tissue from the bulbar conjunctiva onto the cornea. The old belief of regarding pterygium as a chronic degenerative disease with elastotic degeneration caused by ultraviolet irradiation1 has been challenged by several findings. Histopathologically, pterygium also exhibits epithelial hyperplasia and exuberant fibrovascular tissue in the stroma,2–4 in which contractile myofibroblasts are prevalent.5 Importantly, the extent of fibrovascular tissue in the stroma is a reliable morphologic index for predicting the tendency of pterygium recurrence after primary excision.6 Furthermore, intraoperative application of mitomycin C (MMC), an antimetabolite that inhibits cellular proliferation, has been used as an adjunct during pterygium excision.7–9 Collectively, these findings indicate that pterygium is actually a proliferative disease. Laboratory data further showed that ocular surface inflammation may play a pathogenic role in the development of this fibrovascular tissue and hence the progression and recurrence of pterygium. Proinflammatory cytokines such as interleukin-1b and tumor necrosis factor-a can stimulate proliferation of cultured Tenon capsule fibroblasts10 and cause overexpression of matrix-degrading enzymes such as collagenase and stromelysin in cultured pterygium body fibroblasts.11 Furthermore, several potent fibrogenic and angiogenic growth factors have been found in pterygium tissues.12,13 These findings also suggest that control of ocular surface inflammation after pterygium surgery is important in halting pterygium recurrence. In fact, intraoperative and postoperative injections of long-acting steroids11,14 and postoperative injections of 5-fluorouracil (5-FU)14,15 have been advocated to prevent pterygium recurrence. There is little clinical information to corroborate with these laboratory findings in suggesting the potential pathogenic role of ocular surface inflammation in the outcome of pterygium surgery. Specifically, contributing factors and the clinical significance of ocular surface inflammation after pterygium surgery remain largely unknown. To avoid suture-related complications, mostly inflammatory in origin such as granuloma, abscesses, and giant Cornea Volume 27, Number 1, January 2008 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Cornea Volume 27, Number 1, January 2008 papillary conjunctivitis, others have recently used fibrin glue to facilitate conjunctival autograft in pterygium surgery.16–19 Other reported advantages of using fibrin glue include the ease of use, shorter operating times, and less postoperative discomfort.16–19 Pyogenic granuloma, an inflammatory lesion, has been reported after pterygium excision.20–24 However, it remains unclear whether the incidence and pattern of ocular surface inflammation or formation of pyogenic granuloma after pterygium surgery actually differ between fibrin glue and sutures. To address these unknown questions, we retrospectively reviewed our consecutive cases after removal of primary and recurrent pterygia by using amniotic membrane transplantation (AMT) and intraoperative application of MMC and summarized herein our analyses. MATERIALS AND METHODS Patients This study was approved by the institutional review board of Baptist Hospital of Miami/South Miami Hospital (Miami, FL) to retrospectively review the medical records of 23 patients (27 eyes) with primary or recurrent pterygium who were seen at the Ocular Surface Center (Miami, FL) and consecutively operated on with bare sclera excision followed by intraoperative application of MMC and AMT. The first 13 consecutive eyes, operated on from 2002 to 2004, received sutures to attach the amniotic membrane, whereas the next consecutive 14 eyes, operated on from 2005 to 2006, received fibrin glue. Before surgery, possible advantages and disadvantages of the treatment were fully explained to the patients, and their written informed consents were obtained. Clinical data concerning patient demography; preoperative examination including pterygium morphology graded into T1, T2, and T3 as previously described6; surgical procedure; postoperative follow-up; and the final outcome and complications were retrieved from patients’ charts. At the Ocular Surface Center, all surgical procedures have routinely been recorded as digital video, from which the surgical time was calculated. In addition, all patients had documented photographs at each preoperative and postoperative visit; these photographs were evaluated by a masked reader (V.C.). All subjects were followed up for a minimum of 6 months. Surgical Technique All surgical procedures were performed by the same surgeon (S.C.G.T.) to ensure consistency in the extent of tissue removal. Topical anesthesia with 2% lidocaine gel (AstraZeneca, Wilmington, DE) was used for primary cases, and general anesthesia was used for recurrent cases. Several drops of nonpreserved epinephrine 1/1000 (Hospira, Lakes Forest, IL) were instilled to the ocular surface to achieve vasoconstriction for hemostasis. The pterygium area was exposed by 7-0 Vicryl traction sutures placed with episcleral bites at 2–3 mm from the superior and inferior limbus. The pterygium head was undermined and removed from the corneal surface by blunt Inflammation After AMT for Pterygium dissection, and the pterygium body was excised before the semilunar fold. An extensive removal of the subconjunctival fibrovascular tissue was performed to include 3–4 mm beyond and around the pterygium body in primary cases and more extensive removal in recurrent cases. In recurrent cases, the conjunctival tissue was recessed and not resected. The corneal defect area was polished of any residual tissue with a 64 Beaver blade and/or a dental bur. Sponges soaked in 0.04% MMC were applied into the fornix, where the subconjunctival fibrovascular tissue was removed, and care was taken to avoid contact with the bare sclera. After an incubation time of 1– 5 minutes according to the pterygium morphology grade, with a longer duration for T3 but a shorter one for T1, copious irrigation with balanced saline solution was used. Cryopreserved amniotic membrane, obtained from BioTissue (Miami, FL), was peeled off the nitrocellulose filter paper and laid down on the sclera with the stromal surface facing down. In 14 eyes, fibrin glue (Tisseel; Baxter, Irvine, CA) was used to secure the amniotic membrane to the sclera without the use of the provided dual injector. To do so, half of the membrane was folded over onto the other half to expose the stromal surface (Fig. 1A). The fibrinogen solution was first applied to the scleral surface (Fig. 1B) while the thrombin solution was applied to the stromal surface of amniotic membrane that had been exposed through folding (Fig. 1C). The membrane was flipped back on the sclera, and a muscle hook was used to spread the fibrin glue under the amniotic membrane (Fig. 1D). The above steps were repeated for the other half of the membrane. The excessive membrane and fibrin gel were trimmed to flush with the conjunctival edge. In 13 eyes, sutures were used to attach the amniotic membrane. Interrupted 10-0 nylon sutures were placed at the perilimbal bulbar conjunctiva, and 8-0 Vicryl sutures with solid episcleral bites were used at the fornix border, all parallel (not perpendicular) to the incision line. For 6 eyes with recurrent pterygium (5 in the suture group and 1 in the fibrin glue group), a small conjunctival autograft was used in addition to and over the amniotic membrane. At the end of operation, 8–12 mg of triamcinolone acetonide (Bristol-Myers Squibb Company, Princeton, NJ) was injected subconjunctivally in 3 depots in 11 (40.7%) eyes, adjacent to the incision site where the host conjunctiva appeared to be inflamed. Postoperatively, all patients received 1% prednisolone acetate eye drops (Allergan, Irvine, CA) every 2 waking hours for 4–6 weeks and a topical antibiotic for 3–4 weeks. They were examined postoperatively at 1 day, 1 week, 3–4 weeks, and thereafter according to the clinical conditions. Sutures were removed 3–4 weeks after surgery. The presence of conjunctival inflammation was assessed at 3–4 weeks postoperatively and graded as 0 (none), I (mild), II (moderate), and III (severe), as shown in Figure 2. Some eyes with this inflammation received subconjunctival injection of 4–8 mg of triamcinolone acetonide according to the surgeon’s discretion. The grading for inflammation was evaluated before any interventions such as suture removal or steroid injection. For postoperative recurrence of pterygium, a grading system was used on a scale of 1–4 as previously described.25 The operated site was rated as grade 1 if it was normal, as grade 2 if there were fine episcleral vessels but without fibrous tissue, as grade q 2007 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 57 Kheirkhah et al Cornea Volume 27, Number 1, January 2008 FIGURE 1. Surgical steps for AMT with fibrin glue for pterygium. Cryopreserved amniotic membrane was initially laid on the sclera with the stromal surface facing down. Then, half of the membrane was folded over onto the other half to expose the stromal surface (A). The fibrinogen solution was first applied onto the scleral surface (B) while the thrombin solution was applied onto the stromal surface of the amniotic membrane that had been exposed through folding (C). The membrane was flipped back on the sclera, and a muscle hook was used to spread the fibrin glue under the amniotic membrane (D). The above steps were repeated for the other half of the membrane. 3 if fibrovascular tissues reached the limbus, and as grade 4 if fibrovascular tissues invaded the cornea. Statistical Analysis Statistical analysis was performed with SPSS 15 (SPSS, Chicago, IL). For comparison of conjunctival inflammation, pyogenic granuloma, and pterygium recurrence between different subgroups, the Fisher exact test was used. An independent-sample t test was used for comparing the numerical variables between different subgroups including those with sutures or fibrin glue. Multiple logistic regression was used to determine whether the following factors were FIGURE 2. Grading of postoperative host conjunctival inflammation. According to the degree of blood vessel injection, inflammation was graded as grade 0 (no inflammation, A), grade I (mild, B), grade II (moderate, C), and grade III (severe, D). 58 q 2007 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Cornea Volume 27, Number 1, January 2008 Inflammation After AMT for Pterygium associated with the presence of postoperative conjunctival inflammation: age, type of pterygium (primary vs. recurrent), presence of floppy eyelids, duration of intraoperative MMC application, using sutures versus fibrin glue for AMT, and intraoperative injection of triamcinolone acetonide. P # 0.05 was considered statistically significant. RESULTS There were 27 eyes of 23 patients (11 men and 12 women) with a mean age of 53.7 6 16.2 years (range, 29–80 years). Twelve (44.4%) eyes had primary pterygium, and 15 (55.6%) eyes had recurrent pterygium. The number of previous pterygium surgeries in the recurrent group was 1 (8 eyes), 2 (4 eyes), 3 (2 eyes), and 8 (1 eye) times. Among cases with recurrent pterygium, motility restriction with symblepharon was noted in 5 eyes, motility restriction without symblepharon in 1 eye, and symblepharon without motility restriction in 2 eyes. There was no statistically significant difference between the suture group and fibrin glue group regarding the age, type or morphology of pterygium, or intraoperative use of MMC or triamcinolone (Table 1). However, the follow-up period was significantly longer in the suture group than in the fibrin glue group because the former was performed earlier than the latter (Table 1). There was no intraoperative complication in any eyes. Sutures and fibrin glue were used to secure the amniotic TABLE 1. Clinical Findings of Patients With Pterygium and Their Postoperative Complications After Intraoperative Application of MMC and Amniotic Membrane Transplantation With Either Fibrin Glue or Suture Variable Fibrin Glue Suture P No. eyes Age (y) Type of pterygium Primary Recurrent Pterygium morphology T1 T2 T3 Intraoperative MMC (min) Intraoperative triamcinolone Postoperative complications Conjunctival inflammation Grade 0 Grade I Grade II Grade III Postoperative triamcinolone* Pyogenic granuloma Pterygium recurrence Follow-up (mo) 14 58 6 17.3 13 50.7 6 14.7 0.27 7 7 5 8 3 4 7 3.4 6 1.3 7 2 5 6 3.9 6 1.4 4 11 1 0 2 2/3 2 0 14.7 6 5.9 5 3 3 2 5/8 3 2† 45.6 6 8.3 0.34 0.27 0.05 0.72 0.65 0.26 ,0.0001 *Denominator is the number of eyes with conjunctival inflammation. †One eye with grade 3 outcome (conjunctival recurrence) and 1 eye with grade 4 outcome (corneal recurrence). membrane to the underlying sclera in 5 and 7 primary pterygia and in 8 and 7 recurrent pterygia, respectively. The mean surgical time was significantly shorter in eyes with fibrin glue than in eyes with sutures (46.4 6 13.6 vs. 77 6 27.4 minutes, respectively; P = 0.003). Conjunctival epithelial defect over the amniotic membrane healed within 2, 4, and 8 weeks in 5, 5, and 3 eyes with sutures, respectively, and in 4, 8, and 2 eyes with fibrin glue, respectively. There was no statistically significant difference between eyes with fibrin glue or sutures in healing of the epithelial defect within the above time frames (P = 0.27, P = 0.39, and P = 0.40, respectively). No complication such as graft edema or subgraft hematoma was noted postoperatively. The visit at 3–4 weeks after surgery showed that the amniotic membrane–covered area was not inflamed in all these eyes; the surrounding conjunctiva was also not inflamed in 16 eyes (59.3%). However, conjunctival inflammation judged by hyperemia of blood vessels was evident in the remaining 11 (40.7%) eyes and tended to occur around the surgical site and the caruncle in 8 eyes, only the surrounding host conjunctiva in 2 eyes, and only the caruncle in 1 eye. The intensity of such inflammation was greater at the border and gradually faded away from the membrane-covered area. Severity of the inflammation was graded as grade I (mild) in 4 eyes, grade II (moderate) in 3 eyes, and grade III (severe) in 4 eyes (Fig. 2; Table 1). The incidence of such conjunctival inflammation was significantly higher in eyes with sutures than in those with fibrin glue [8/13 (61.5%) vs. 3/14 (21.4%), respectively, P = 0.05]. Regression analysis revealed that only the use of sutures was significantly associated with postoperative conjunctival inflammation (P = 0.05), whereas other factors such as age, type of pterygium (primary vs. recurrent), presence of floppy eyelids, duration of intraoperative MMC application, and intraoperative injection of triamcinolone acetonide were not. Correlation of surgical outcome with postoperative conjunctival inflammation is shown in Figure 3. During the follow-up of 29.6 6 17.2 months (range, 6–56 months) after surgery, no recurrence was noted in 16 eyes without conjunctival inflammation; all showed grade 1 or 2 outcomes (Figs. 4A–C). On the other hand, 7 of 11 eyes with conjunctival inflammation received subconjunctival injection of triamcinolone at the time of detection, namely, 3–4 weeks after surgery. After injection, inflammation resolved in all these 7 eyes without development of recurrence, pyogenic granuloma, or transient increase of intraocular pressure (Figs. 4D, E). The remaining 4 eyes with grade I (2 eyes), grade II (1 eye), and grade III (1 eye) conjunctival inflammation did not receive subconjunctival steroid injections. The 2 eyes with grade I inflammation subsequently developed pyogenic granuloma and 1 of them developed grade 3 outcome with conjunctival recurrence after 7 months (Figs. 4F–I). The eye with grade II inflammation developed grade 4 outcome with corneal recurrence after 4 months; the eye with grade III inflammation developed pyogenic granuloma (Figs. 5A–C). Therefore, pyogenic granuloma developed in 3 (75%) of 4 eyes with untreated postoperative inflammation compared with 2 (8.7%) of 23 eyes without inflammation or with treated inflammation (P = 0.01; Figs. 5D–F). In these 5 eyes with pyogenic granuloma, the lesions were all found around the caruncle q 2007 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 59 Cornea Volume 27, Number 1, January 2008 Kheirkhah et al FIGURE 3. Correlation of surgical outcome with postoperative conjunctival inflammation. Surgery with intraoperative application of MMC and AMT was done for 27 eyes with primary or recurrent pterygia. Examination at 3–4 weeks after surgery revealed lack of conjunctival inflammation around the surgical site in 16 eyes and the presence of such inflammation in other 11 eyes. During postoperative follow-up, no recurrence of pterygium but 2 pyogenic granulomas occurred in the 16 eyes without this inflammation. Of 11 eyes with such inflammation, 7 received subconjunctival triamcinolone injection, whereas 4 did not. No complication was noted in the former eyes, but 2 pterygium recurrences and 3 pyogenic granulomas developed in the latter eyes. area, but were not associated with suture location, and developed 6.6 6 2.2 weeks (range, 3–8 weeks) after surgery. Incidences of the above complications in eyes with fibrin glue or sutures are summarized in Table 1. DISCUSSION Postoperative conjunctival inflammation, defined by injection of blood vessels, is common after any ocular surface surgeries and is usually regarded as a normal wound healing response. Consequently, its frequency and significance might have been overlooked in pterygium excision. When judged at 3rd–4th postoperative weeks, a period sufficient to allow normal inflammatory responses to subside, host conjunctival inflammation with various intensities was still present in 40% of eyes in this study despite intraoperative application of MMC and AMT. At that time, conjunctival inflammation was accentuated at the border and faded from there (Figs. 2 and 4), a finding noted previously,21,25 whereas the amniotic membrane–covered area was noninflamed. Similar host conjunctival inflammation has also been described in some eyes receiving AMT for conjunctivochalasis and fornix reconstruction for other cicatricial diseases.26–28 It remains unclear whether such inflammation is contingent on certain diseases or eye conditions. Nevertheless, its incidence might be higher if pterygium excision is not accompanied by transplantation of amniotic membrane, which is known to exert anti-inflammatory and antiangiogenic actions.29 One may also suspect that its incidence is higher without MMC, of which one known pharmacologic action is to reduce vascularity in the treated area. On the other hand, at postoperative 3–4 weeks, transient conjunctival hyperemia and chemosis frequently occur in eyes receiving conjunctival autograft before remitting to a quiet surface.30 60 Bekibele et al31 also noted significant early postoperative inflammation at 2 weeks after pterygium surgery by using 80 silk sutures in 17.1% of 33 cases using conjunctival autograft. Although a multitude of factors might contribute to postsurgical conjunctival inflammation, our study identified the use of sutures as the only significant risk factor among others examined. Incidence of the inflammation was significantly higher in eyes using sutures than in those receiving fibrin glue (61.5% vs. 21.4%, respectively). Sutures as foreign bodies elicit inflammation in any eye surgeries. Naturally, they could aggravate inflammation in eyes with pterygium after surgery. The use of fibrin glue for conjunctival autograft in pterygium surgery reveals several advantages including a shorter operating time, increased postoperative comfort, and avoiding other suture-related complications such as buttonholes, suture abscesses, tissue necrosis, and giant papillary conjunctivitis.17–19,32 Our study was the first showing that conjunctival inflammation was significantly reduced by fibrin glue in lieu of sutures in pterygium surgery using cryopreserved amniotic membrane. Furthermore, the surgical time was shortened by fibrin glue, allowing topical anesthesia for at least primary pterygium. Clinical significance of prolonged conjunctival inflammation was revealed by correlating it with the postoperative outcome (Fig. 3). As stated in the introduction, ocular surface inflammation could play a significant pathogenic role not only in pathogenesis of primary pterygium but also in progression of recurrence. A satisfactory aesthetic outcome (grades 1 and 2) was noted in all 16 eyes that did not manifest conjunctival inflammation at 3–4 postoperative weeks and in 7 eyes whose inflammation was treated with subconjunctival steroid injections. In contrast, 1 eye with conjunctival recurrence (grade 3) and 1 eye with corneal recurrence (grade 4) were noted among q 2007 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Cornea Volume 27, Number 1, January 2008 Inflammation After AMT for Pterygium FIGURE 4. Correlation of surgical outcome with control of postoperative conjunctival inflammation: case examples. An eye with recurrent pterygium with symblepharon and restricted motility after 8 pterygium excisions (A) underwent surgery by using sutures. Four weeks after surgery (B), there was no sign of host conjunctival inflammation. This eye showed grade 1 outcome with restoration of full ocular motility at 4 years postoperatively (C). Three weeks after surgery with fibrin glue for a primary pterygium (D), the amniotic membrane–covered surgical area was not inflamed; however, moderate inflammation (grade II) was noted in the surrounding host conjunctiva. Subconjunctival injection of triamcinolone resulted in a smooth and quiet ocular surface with grade 1 outcome 4 months after surgery (E). Another eye with primary pterygium (F) underwent surgery by using sutures. Four weeks after surgery (G), mild inflammation (grade I) was visible only in the caruncle, but triamcinolone was not injected. This inflammation gradually developed into grade 3 conjunctival recurrence, as shown at 3.5 (H) and 7 months (I) after surgery. 4 eyes with untreated postoperative conjunctival inflammation, with sutures being used in both these eyes. When sutures were used, Solomon et al21 noted conjunctival inflammation in 17 (31.5%) of 54 eyes within 3 postoperative months after pterygium excision with AMT but without MMC. Intriguingly, their life table analysis showed delayed recurrences, ie, after 3 months. Herein, we also noted that grade 3 and grade 4 recurrences occurred at 7 and 4 months after surgery, respectively (Fig. 4). It is also known that a follow-up period for as long as 1 year is needed to determine whether corneal recurrences will develop.35 Collectively, these findings prompted us to speculate that persistent postoperative conjunctival inflammation, if not halted, might lead to conjunctival and corneal recurrences after pterygium surgery. The above hypothesis calls for taking preoperative, intraoperative, and postoperative measures to prevent and/or treat the conjunctival inflammation to improve the surgical outcome of pterygium surgery. Postoperatively, it is prudent to eradicate causes such as dry eye, which may stir up ocular surface inflammation.33,34 Adjunctive therapies such as intraoperative MMC or 5-FU or postoperative b-irradiation or 5-FU are needed in bare sclera excision of pterygium if a conjunctival autograft is not used. Even if a conjunctival autograft is performed with sutures, Yaisawang and Piyapattanakorn36 noted a higher recurrence rate in patients who received inadequate postoperative topical corticosteroids. We previously reported that AMT without such adjunctive therapies did not achieve the same outcome as conjunctival autograft in q 2007 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 61 Kheirkhah et al Cornea Volume 27, Number 1, January 2008 FIGURE 5. Pyogenic granuloma after pterygium surgery. An eye with primary pterygium (A) underwent surgery with AMT by using sutures. Three weeks postoperatively (B), severe conjunctival inflammation (grade III) was noticed in the host conjunctiva. Without steroid injection, a pyogenic granuloma was visible in the caruncle 6 weeks after surgery (C). An eye with recurrent pterygium (D) underwent surgery with AMT by using sutures. Conjunctival inflammation was absent 4 weeks postoperatively (E), but a pyogenic granuloma was evident at 8 weeks after surgery (F). primary pterygium.25 We subsequently found that sublesional injection of triamcinolone resulted in resolution of increased fibrovascular or inflammatory activity in 12 of 17 eyes that manifested grade 3 outcome at the postoperative 3 months, giving rise to the same outcome as conjunctival autograft for primary pterygium.21 The latter finding was confirmed by a recent study by Prabhasawat et al,14 who also found that sublesional injection of 5-FU was equally effective, and both were significantly more effective than topical steroid alone in halting progression to grade 4 corneal recurrence. Herein, we noted that such inflammation was more prevalent in the suture group and best aborted at an earlier stage, ie, postoperative 3–4 weeks, by subconjunctival injection of triamcinolone before any fibrovascular tissue ingrows into the amniotic membrane– covered area. This notion was supported by the finding that all eyes with such injection resulted in grade 1 or 2 outcomes. On the other hand, 2 of 4 eyes without injection developed conjunctival and corneal recurrences. Further study is needed to elucidate how anti-inflammatory and antifibrotic therapies may halt pterygium recurrence by aborting host tissue inflammation. Pyogenic granuloma is thought to be an inflammatory conjunctival lesion, but it is neither pyogenic nor granulomatous. It may occur when minor trauma or surgery stimulates exuberant healing with fibrovascular proliferation, although the exact underlying triggering factors remain obscured. Pyogenic granuloma has been recognized as a postoperative complication after pterygium surgery, with incidences reaching up to 40%, 7.9%, and 9.2% when bare sclera excision is 62 accompanied by intraoperative application of MMC, conjunctival autograft, and AMT, respectively.20–22 An earlier study did not show any correlation between its incidence and wound closure with sutures or without.37 In our study, conjunctival pyogenic granuloma, diagnosed solely by clinical observation, developed in 5 (18.5%) of 27 eyes, seemingly higher than that in our earlier experiences where AMT was performed without MMC.21 Importantly, all pyogenic granulomas were located around the caruncle, developed within 2 months after surgery, and unlike conjunctival inflammation, occurred equally in both suture and fibrin glue groups. Although impaired wound closure, delayed apposition, chronic irritation, and incomplete removal of the Tenon capsule have been implicated as causes of this complication,22,38 none were apparent in our series. However, the incidence of pyogenic granuloma was significantly higher in eyes with untreated host conjunctival inflammation than in those without inflammation or in eyes whose inflammation had been treated with injection of triamcinolone. Further research is necessary to determine the pathogenesis of this seemingly higher incidence of pyogenic granuloma around the caruncle and its effect on the long-term outcome. Previously, we reported that AMT was inferior to conjunctival autograft with sutures but without intraoperative MMC for recurrent pterygia,21,25 a finding that was also noted recently by others.24,39 Nevertheless, in the current study, a similar satisfactory aesthetic outcome with total restoration of ocular motility was achieved in 7 eyes with recurrent and multirecurrent pterygia by AMT with fibrin glue and intraoperative MMC together with early subconjunctival injection q 2007 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Cornea Volume 27, Number 1, January 2008 of triamcinolone to control postoperative conjunctival inflammation. Although our data analyses were from serial digital photographs and digital video recordings of surgical procedures, one’s enthusiasm is understandably dampened by several limitations of this study such as a relatively small sample size and its being retrospective and uncontrolled. Furthermore, a higher incidence of pterygium recurrence in the suture group may be attributed to a longer follow-up time. This concern is negated by the fact that the mean follow-up for both groups was .12 months, an interval in which most cases of pterygium recurrences are expected to have developed.35 To resolve these potential drawbacks, future prospective controlled studies designed to focus on the corneal early control of host conjunctival inflammation may not only clarify the pathogenesis of pterygium recurrence but also help formulate a better strategy for managing other forms of cicatricial keratoconjunctivitis of the ocular surface. REFERENCES 1. Austin P, Jakobiec FA, Iwamoto T. 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