Cauterized conjunctival autograft with and without mitomycin C in primary pterygium surgery

Hesham A Enany; Tamer G Elsayed; Reem A.K Dessouky

doi:10.4103/ejos.ejos_79_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 116 | Issue : 1 | Page : 28-33

Cauterized conjunctival autograft with and without mitomycin C in primary pterygium surgery

Hesham A Enany, Tamer G Elsayed, Reem A.K Dessouky
Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission	25-Oct-2022
Date of Decision	18-Nov-2022
Date of Acceptance	26-Nov-2022
Date of Web Publication	30-Mar-2023

Correspondence Address:
MD Reem A.K Dessouky
Department of Ophthalmology, Faculty of Medicine, Zagazig University, Zagazig 44519, AlSharkia
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ejos.ejos_79_22

Abstract

Aim To compare between the outcomes of cauterized conjunctival autograft (CA) with and without mitomycin C (MMC) in primary pterygium surgery.
Patients and methods This prospective interventional comparative study included 50 eyes in 50 patients with primary pterygium. Patients were randomly assigned into two equal groups: group 1 underwent pterygium excision with cauterized CA fixation, and group 2 underwent pterygium excision with cauterized CA fixation and intraoperative application of 0.02% MMC for 3 min. All patients underwent a preoperative, first day, first week, first month, third month, and sixth month postoperative ophthalmic examination. Any intraoperative or postoperative complications were recorded. Primary outcomes were reported as incidence of recurrence and any major (sight threatening) complications. Secondary outcomes were reported as any minor complications.
Results A total of 50 patients (28 males and 22 females, with male to female ratio 1 : 1.3) were included in this study. Complications encountered in our study included recurrence of pterygium, which occurred in one (4%) eye in group 1 and 0 eyes in group 2. Two (8%) eyes in group 1 versus one (4%) eye in group 2 showed subconjunctival hemorrhage, one (4%) eye in group 2 showed focal scleral thinning, and one (4%) eye in group 2 showed a corneal epithelial defect. There was no statistically significant difference between the two groups regarding the incidence of any complication (P>0.05).
Conclusion Cauterized CA without MMC is a safe and effective procedure for the surgical treatment of primary pterygium. There was no added benefit to intraoperative MMC application.

Keywords: autograft, cauterized, mitomycin C, pterygium

How to cite this article:
Enany HA, Elsayed TG, Dessouky RA. Cauterized conjunctival autograft with and without mitomycin C in primary pterygium surgery. J Egypt Ophthalmol Soc 2023;116:28-33

How to cite this URL:
Enany HA, Elsayed TG, Dessouky RA. Cauterized conjunctival autograft with and without mitomycin C in primary pterygium surgery. J Egypt Ophthalmol Soc [serial online] 2023 [cited 2023 May 30];116:28-33. Available from: http://www.jeos.eg.net/text.asp?2023/116/1/28/372947

Introduction

Pterygium is a common degenerative disease worldwide, and its occurrence increases with prolonged exposure to ultraviolet rays, and air pollutants, in addition to proposed hereditary and immunological factors [1]. Although the surgical technique of pterygium excision is relatively simple, surgical results can be disappointing owing to high recurrence rates. Recurrence not only annoys the patient cosmetically but also makes another intervention more difficult [2]. Therefore, many adjuncts have been added to the simple removal of primary pterygium. Nowadays, mitomycin C (MMC) application and conjunctival autograft (CA) transplantation are commonly used [3].

MMC prevents pterygium recurrence by its antiproliferative action, which inhibits the formation of fibroblast and collagen. It has been documented that intraoperative application of MMC is effective and more safe than postoperative topical use. This is because single application avoids toxicity owing to cumulative dosage [4]. Recurrence rates with the use of intraoperative MMC after pterygium excision range from 3 to 38%. Variable results are in part owing to different concentrations and durations used in the studies [3]. Unfortunately, the minimum effective dose that can minimize recurrence without inducing complications is so far not known [5].

The mechanism of action of CA is less well understood, most authors attribute it to the theory of contact inhibition. In addition, CA including limbal stem cells helps return the normal barrier function of the limbus [5]. Even though this technique is more difficult and time consuming, it is still favored by many surgeons owing to its high safety profile. Recurrence rates with CA range from 2 to 39% [6]. Different sutureless techniques of graft fixation were introduced to decrease the operative time. Cautery fixation has proven to be effective with a similar recurrence rate [7].

Studies comparing MMC and CA in primary pterygium surgery showed lower recurrence rates and less complications with CA fixation [3]. These results suggested that the combination of both techniques could provide better safety and efficacy. Therefore, the aim of this study was to compare the outcomes of cauterized CA with and without MMC in primary pterygium surgery.

Patients and methods

This is a prospective comparative randomized study that was conducted in the Al-Fath Eye Hospital, Zagazig, Egypt. The study was approved by the Institutional Review Board and Ethical Committee and adhered to the tenets of Helsinki Declaration. A total of 63 patients attended the outpatient clinic complaining of pterygium requiring surgical intervention during the period from April 2019 to April 2020. Patients’ demographic data were recorded followed by detailed history taking and ophthalmic examination. Pterygia were graded based on translucency [8] as follows: T1 atrophic pterygium, T2 intermediate pterygium (causing partial obscuration of the episcleral vessels), and T3 fleshy pterygium (completely obscuring the episcleral vessels). Inclusion criteria were adults with progressive primary pterygia invading more than 2 mm of the cornea causing altered visual acuity and/or irritation. Exclusion criteria were recurrent pterygium, prior eye surgery, any ocular surface abnormality (e.g. dry eye, connective tissue disorders, or chronic use of topical antiglaucoma drugs), or patients refusing to participate in the study. After excluding eyes that did not meet the criteria of our study, 50 eyes in 50 patients were included. A detailed informed consent was obtained from all patients before enrollment in the study. Participants were randomly assigned to one of two groups according to the intraoperative use of MMC: group 1, in which the pterygium was excised with cauterization of CA without use of MMC, and group 2, in which pterygium was excised with cauterization of CA with intraoperative application of 0.02% MMC for 3 min.

Methods ([Figure 1])

All surgeries were performed by the same surgeon (an Ophthalmology consultant with 20 years of experience) who recorded all standard preoperative preparation and performed and recorded all operative steps (including any intraoperative complications).

Figure 1 (a) Preoperative primary pterygium, (b) cutting of pterygium head, (c) dissecting pterygium body, (d) pterygium removed, (e) measuring recipient graft area, (f) dissecting donor area, (g) graft completely dissected, (h) alignment of graft in recipient area, and (i) cauterizing graft edge.

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Preoperative preparation

All patients were operated under local anesthesia in the form of topical 0.4% benoxinate hydrochloride [Benox, EIPICO, 10th of Ramadan city, Egypt Alcon Couvreur, Puurs-Sint-Amands, Belgium] and subconjunctival injection of 1 ml of a mixture of 2% lidocaine (Sigma-Tec Pharmaceutical Industries Corp, 6th of October City, Egypt) and 1 : 100 000 adrenaline (Chemical Industries Development ‘CID,’ Giza, Egypt). The eyelid and periorbital skin were sterilized, and then sterile draping and a speculum were placed.

Operative procedure

The pterygium head was detached from the cornea. The body of the pterygium consisting of pathological conjunctiva and underlying fibrovascular tissue was dissected from the underlying sclera and removed with Wescott scissors. The cornea was scraped clean using a sharp blade 15. Any bleeding from the scleral bed was controlled by pressure with cotton buds. In group 2, MMC was applied to the bare scleral area by a piece of sponge soaked in MMC (0.02% concentration) for a duration of 3 min. The sclera was then washed copiously with at least 150 ml of balanced salt solution.

The area of conjunctival defect was measured by caliper. The autograft was obtained from the superior limbal conjunctiva and was measured 1 mm larger than the defect to overcome the expected retraction after cauterization. Overall, 0.5 ml of lidocaine-epinephrine mixture was injected just beneath the conjunctiva at 12 o’clock position. The autograft was freed by meticulous dissection of the conjunctiva from the Tenon capsule beneath. The conjunctival graft was positioned on the bare sclera with care taken to maintain correct limbal and epithelial orientation. Donor site was left without sutures.

Cauterization of the autograft was performed with a bipolar cautery (YZ-II; Shanmu, Dalian, China) in the graft corners. The aim was subtle whitening of the conjunctiva. The procedure was repeated on the rest of the graft edges at equidistant intervals to reach a total of seven to eight cautery points. Lastly, the speculum was removed, and graft stability while blinking was confirmed. At the end of surgery, polymyxin B sulfate-neomycin sulfate-dexamethasone (Maxitrol, Alcon-Couvreur, Belgium) eye drops were applied, and an ocular patch was placed.

Postoperative measures

The patch was removed 24 h after surgery. Polymyxin B sulfate-neomycin sulfate-dexamethasone eye drops were applied four times daily and tobramycin-dexamethasone (TobraDex, Alcon-Couvreur, Belgium) ointment twice daily during the first postoperative week. Both eye drops and ointment were gradually tapered to be stopped by 1 month. A tear substitute (Tears Naturale, Alcon-Couvreur, Belgium) was prescribed twice daily for 1 month. Oral analgesia, paracetamol 500 mg tablets, was added as needed.

Evaluation and follow-up

Patients were followed up 24 h postoperatively and then consecutively at 1 week, 1, 3, and 6 months by a full ophthalmic examination. In case of complications, more frequent follow-up visits were scheduled. Primary outcome measures were pterygium recurrence and any major (sight threatening) complications. Recurrence was defined as regrowth of fibrovascular tissue from the pterygium site invading the cornea for more than 1 mm. Secondary outcome measures included any reported minor complications.

Statistical methods

All statistical analyses were done using SPSS, version 23 statistical software (SPSS, Inc., Chicago, Illinois, USA). Quantitative variables (mean, SD, frequencies) were analyzed using Student’s t test. Qualitative variables were reported using descriptive statistics (χ² test). A P value of less than equal to 0.05 was considered statistically significant.

Results

This study included 50 eyes in 50 patients divided into two equal groups. Group 1 included 25 eyes treated with cauterized CA. Group 2 included 25 eyes treated with cauterized CA and intraoperative 0.02% MMC for 3 min. The mean age of the patients in group 1 was 46.5±8.11 years and in group 2 was 48.2±9.12 years. Group 1 included 15 males and 10 females (male to female ratio=1.5 : 1), whereas group 2 included 13 males and 12 females (male to female ratio=1.1 : 1). There was no statistically significant difference between the groups regarding demographic data (P>0.05) ([Table 1]).

Table 1 Demographic distribution among the two studied groups

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Two (8%) eyes in group 1 and one (4%) eye in group 2 showed intraoperative subconjunctival hemorrhage under the graft. Patients were followed up weekly for spontaneous resolution. This occurred by 1 month without any adverse effect on the graft. The difference in occurrence of subconjunctival hemorrhage was not statistically significant (P>0.05) ([Table 2]).

Table 2 Incidence of complications in the two study groups

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All patients showed complete corneal healing after 1 week of surgery except for one (4%) eye in group 2. The patient presented with increased lacrimation and discomfort. A corneal epithelial defect related to the site of surgery was detected with fluorescein stain. The frequency of topical lubricants was increased, and total corneal epithelialization was achieved by the second week. There was no statistically significant difference in the incidence of corneal healing complications between the groups (P>0.05) ([Table 2]).

One (4%) eye in group 2 showed focal scleral thinning (partial melt) with uveal exposure at the site of MMC application ([Figure 2]). This appeared at the first postoperative month. The patient was given both oral and topical steroids, and weekly follow-up visits were scheduled. This was successful in arresting progression of the scleral melt, and no surgical intervention was required. This complication was not seen in group 1. The difference in incidence of scleral thinning between groups was not statistically significant (P>0.05) ([Table 2]).

Figure 2 Focal scleral thinning in a patient in group 2 (CA+MMC). CA, conjunctival autograft; MMC, mitomycin C.

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Recurrence of pterygium occurred in one (4%) eye in group 1. This was observed at 6 months postoperatively. No recurrence was recorded in group 2. The difference between the two groups was not statistically significant regarding pterygium recurrence (P>0.05) ([Table 2]).

Discussion

Surgical removal of pterygium is the mainstay of treatment; however, the risk of recurrence remains a challenge. Various surgical techniques have been introduced to overcome this problem [9]. CA placement is effective but requires suturing, prolonging surgery and causing discomfort [10]. Cautery fixation of the graft is efficient and causes minimal pain [7]. MMC is an antimetabolite used to reduce pterygium recurrence. Reports of dreadful ocular complications remain a concern [11]. Intraoperative application of low-dose MMC for 2–5 min is effective and safe [2]. The combination of both methods may reduce recurrence rates without added side effects.

In the presence of a CA, the dose of MMC can be lowered, thus avoiding its complications, and making it safer to use. The different modes of action can further decrease recurrence rates. We therefore conducted this study to compare the outcomes of CA fixation with and without MMC in primary pterygium.

Sutureless graft fixation methods are more rapid than suturing technique. Cautery autograft fixation, in specific, has proven to be safe, effective, and associated with the least irritation postoperatively [12]. This encouraged us to use cauterization to fix the graft as the combination of MMC and CA would definitely prolong the time of surgery.

In our study, we recorded recurrence of pterygium in one (4%) eye in group 1 (CA only). Recurrence was not seen in group 2 (MMC+CA). The difference between the two groups was not statistically significant (P=0.31). Our findings are consistent with similar studies comparing the two techniques. Both Wong and Law [13] and Agahan et al. [14] concluded that there was no significant difference in recurrence rates between CA and MMC versus CA alone in primary pterygium surgery (P=0.5 and 0.53, respectively). On the contrary, Frucht-Pery et al. [15] reported a statistically significant decrease in recurrence rates when combining CA with MMC when compared with CA alone (P=0.038). This is probably due to the difference in the criteria of recurrence between our study and theirs. They defined recurrence as any invasion of blood vessels through the limbus into the clear cornea, whereas we considered recurrence as invasion of fibrovascular tissue for more than 1 mm into the cornea.

Similarly, Frucht-Pery et al. [15] and Agahan et al. [14] reported no recurrence in eyes that received both CA and MMC after primary pterygium excision. Segev et al. [4] recorded only one (2%) case of recurrence after pterygium excision with intraoperative MMC 0.02% for 2 min and limbal CA. They believed recurrence was due to the young age of the patient in which recurrence had previously occurred, further describing the pterygium to be clinically nonsignificant and stable for more than one year. We attribute our low recurrence rate throughout the study to the surgeon’s experience and adequate surgical technique. In a study conducted by Oke et al. [16], they found that surgical experience affected the outcome of pterygium surgery. Surgical techniques involving excessive suturing, small conjunctival graft size, remnant Tenon tissue, and graft retraction increase the likelihood of recurrence [2], while cauterization to fix the graft, meticulous dissection from Tenon capsule, and adequate graft size all contributed to satisfactory results in this study.

Other reported complications in our study included subconjunctival hemorrhage, persistent corneal epithelial defect, and focal scleral thinning. Subconjunctival hemorrhage appeared in two (8%) eyes in group 1 and one (4%) eye in group 2. We preferred to control intraoperative bleeding from the scleral bed with local pressure and not cautery. Our rationale was to avoid surgically induced scleral necrosis from the additive effect of both excessive cautery and MMC. Although this did not affect intraoperative visualization, it may account for the postoperative development of subconjunctival hemorrhage. Nevertheless, hemorrhage resolved in all cases as in previous studies by Frucht-Pery et al. [15] and Segev et al. [4], who also reported subconjunctival hemorrhage resolving without any adverse effects.

We encountered a persistent corneal epithelial defect in one (4%) eye in group 2, which healed completely with the use of excessive lubricants. This was probably owing to MMC as it occurred at the site of the excised pterygium. Agahan et al. [14] reported superficial punctate keratitis in one eye in their study which was also treated by a topical lubricant.

Additionally, we reported focal scleral thinning with uveal exposure in one (4%) eye in group 2 which we believe occurred owing to the application of MMC. Scleral melt is a well-known adverse effect of MMC use and has been reported even with single intraoperative use [17]. The scleral melt developed 1 month after surgery and was well controlled with topical and oral steroids. Frucht-Pery et al. [15] also reported partial melting of the conjunctival transplant in one eye that received CA and MMC. It was successfully treated with frequent topical corticosteroids and eye patching.Other complications such as granuloma formation, Tenon cyst, and graft shrinkage/displacement were not reported in this study. This is mainly due to sutureless graft fixation and appropriate surgical technique. Adequate dissection of the CA from the underlying Tenon capsule and complete excision of any remnants of Tenon at the site of the excised pterygium avoid formation of Tenon cyst [18]. Proper apposition of the edges of the transplant to the surrounding conjunctiva with equal tension allows rapid vascularization [19] and optimal healing of the graft without granuloma formation [18]. Moreover, the absence of sutures decreases the incidence of granuloma formation.

This study showed that both CA alone and CA with MMC are equally effective in primary pterygium surgery. The addition of MMC to CA did not significantly lower the recurrence rates. MMC carries a higher risk of inducing sight-threatening complications. The main limitation of this study is the short postoperative follow-up. Although most pterygium recurrence occurs within the first six months in cases with CA, it may appear late at 36 months with MMC application [16]. Longer follow-up is recommended to detect the occurrence of late recurrence and adverse effects.

In conclusion, combining MMC with CA transplantation did not improve the outcomes of primary pterygium surgery. It is better not to add MMC owing to its potential harmful effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Palewski M, Budnik A, Lisowski Ł, Konopińska J. Evaluation of the efficacy of different pterygium surgeries in Polish caucasian population. J Ophthalmol 2022; 2022:1–5.
2.	Ghiasian L, Samavat B, Hadi Y, Arbab M, Abolfathzadeh N. Recurrent pterygium: a review. J Curr Ophthalmol 2021; 33:367–378.
3.	Shahraki T, Arabi A, Feizi S. Pterygium: an update on pathophysiology, clinical features, and management. Ther Adv Ophthalmol 2021; 13:251584142110201.
4.	Segev F, Jaeger-Roshu S, Gefen-Carmi N, Assia EI. Combined mitomycin C application and free flap conjunctival autograft in pterygium surgery. Cornea 2003; 22:598–603.
5.	Sarkar P, Tripathy K. Pterygium. Treasure Island, FL: StatPearls Publishing; 2021.
6.	Sánchez-Cajiao JP, Sánchez-Barahona JD, Jaimes Y, Rodríguez-Darabos EI, Pérez-Gutiérrez N. Pterygium surgery with conjunctival limbal autograft in an eye clinic from Villavicencio, Colombia. Rev brasoftalmol 2022; 81:e 0019.
7.	Lešin M, Paradžik M, Marin Lovrić J, Olujić I, Ljubić Ž, Vučinović A et al. Cauterisation versus fibrin glue for conjunctival autografting in primary pterygium surgery (CAGE CUP): study protocol of a randomised controlled trial. BMJ Open 2018; 8:e020714.
8.	Tan DTH, Chee SP, Dear KBG, Lim ASM. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision. Arch Ophthalmol 1997; 115:1235–1240.
9.	Elshreef OKI, Abdel wahab AM, Abu Elaish MH. Comparison between conjunctival autograft and intraoperative mitomycin C in surgical treatment of pterygium according to the recurrence rate. J Recent Adv Med 2021;2:104–111.
10.	Mejia L, Gil J. Use of amniotic membrane ameliorating postoperative discomfort in pterygium surgery. Pan Am J Ophthalmol 2022; 4:18. [Full text]
11.	Balakrishna N, F Tasneem A, I Nayak V, N. K, Niharika Prasad S. Randomised controlled study of amniotic membrane graft versus conjunctival autograft in primary pterygium excision. IP Int J Ocul Oncol Oculoplasty 2020; 6:33–41.
12.	Mejía LF, Santamaría JP, Cuevas M, Córdoba A, Carvajal SA. Comparison of 4 techniques for limbal-conjunctival autograft fixation in primary pterygium Surgery. Eur J Ophthalmol 2017; 27:466–469.
13.	Wong VA, Law FCH. Use of mitomycin C with conjunctival autograft in pterygium surgery in Asian-Canadians. Ophthalmology 1999; 106:1512–1515.
14.	Agahan ALD, Astudillo PP, Dela Cruz RC, Oftalmologico S, Rizal J, Hospital PG. Comparative study on the use of conjunctival autograft with or without mitomycin C in pterygium surgery. Philipp J Ophthalmol Orig Artic Philipp J Ophthalmol 2014; 39:73–77.
15.	Frucht-Pery J, Raiskup F, Ilsar M, Landau D, Orucov F, Solomon A. Conjunctival autografting combined with low-dose mitomycin C for prevention of primary pterygium recurrence. Am J Ophthalmol 2006; 141:6.
16.	Oke I, Hall N, Elze T, Miller JW, Lorch AC, Hunter DG et al. Risk factors associated with pterygium reoperation in the IRIS registry. JAMA Ophthalmol 2022; 1:1138–1141.
17.	Dougherty PJ, Hardten DR, Lindstrom RL. Corneoscleral melt after pterygium surgery using a single intraoperative application of mitomycin-C. Cornea 1996;15:537–40.
18.	Kodavoor S, Preethi V, Dandapani R. Profile of complications in pterygium surgery − a retrospective analysis. Indian J Ophthalmol 2021; 69:1697.
19.	Ghoz N, Elalfy M, Said D, Dua H. Healing of autologous conjunctival grafts in pterygium surgery. Acta Ophthalmol 2018; 96:e979–e988.