Preoperative Versus Intraoperative Subpterygial Mitomycin C Injection for Prevention of Pterygium Recurrence

Abstract

Purpose:

To evaluate postoperative outcome and recurrence rate after primary pterygium excision using preoperative versus intraoperative subpterygial Mitomycin C (MMC) injection.

Methods:

Eighty-three eyes with primary pterygium were divided into 2 groups. Group A (35 eyes) was operated upon with pterygium excision 5 min after subpterygial injection of 0.1 mL 0.015% MMC in the same operative setting. Group B (48 eyes) was operated upon with pterygium excision 1 month after subpterygial injection of the same amount and concentration of MMC as in group A. Pterygium regrowth over the cornea for 1 mm or more was considered as a recurrence.

Results:

The mean follow-up was 30.66±4.48 months in group A and 29.5±4.3 months in group B. In group A, the reported recurrence rate was 5.7%, while it was 4.2% in group B. No serious postoperative complications were reported. There was no statistically significant difference between both groups regarding the recurrence rate as well as the complication rate.

Conclusion:

Both techniques proved to be effective in reducing the recurrence rate after excision of primary nasal pterygium with minimal postoperative complications, with no need of a second surgery for patients in group A.

Introduction

Due to the high recurrence rates (30%–80%) after pterygium excision using the bare sclera technique, a variety of other treatment modalities have been proposed.¹ Adjunctive treatment after a bare sclera excision with topical mitomycin C (MMC) is effective in reducing the recurrence rate (0.5%–16%).^2–4 However, site-threatening side effects after topical MMC have raised a major concern about its topical application.⁵

In an attempt to decrease the ocular surface exposure to topical MMC, a subpterygial injection of MMC has been proposed by many authors studying its effect on the recurrence rate.^6–8 In a previous work, we investigated the recurrence rate after preoperative subpterygial injection of MMC 0.015% 1 month before the pterygium excision and proved effective.⁹ However, this technique needs 2 operative sessions, which may not be desirable by some patients. Therefore, in this work, we injected MMC in the subpterygial tissue before pterygium excision in the same operative session.

We present our experience for control of postoperative pterygium recurrence by using subpterygial MMC injection using 2 different techniques on 2 groups of patients with primary nasal pterygia. Then, we compared the postoperative outcome in both groups.

Methods

This was a prospective randomized study conducted on 83 eyes of 83 patients with primary nasal pterygium, who attended the health service in Menoufia University Hospitals in Shebin El Kom and Manshiet Soltan during the period between January 2009 and January 2013.

The patients were randomly enrolled into 2 groups. The first group A underwent an injection of 0.1 mL of 0.15 mg/mL MMC into the body of pterygium that was removed 5 min later in the same operative session. The second group B underwent an injection of the same amount and concentration of MMC in the body of pterygium 1 month before surgical excision. In both groups, the primary pterygium was removed using the bare scleral technique.

All patients of the study had a primary nasal pterygium encroached on the surface of the cornea with no other ocular pathology. A comprehensive ophthalmic examination, including best-corrected visual acuity testing, slit-lamp examination, Goldmann applanation tonometry, fundus examination, and examination of ocular motility, was carried out for all patients. Consents were taken from all patients and research was approved by the institutional review board. All measures were in accordance with the tenets of the Declaration of Helsinki.

Surgical technique

Preparation of MMC

Mutamycin (Bristol-Myers-Squibb) vial containing 5 mg powder of mitomycin was reconstituted with 33 mL balanced salt solution to get a concentration of 0.15 mg/mL for injection.

Technique of MMC injection

In both groups, topical anesthesia (benoxinate hydrochloride 0.4%) was first applied in the involved eye followed by a subconjunctival injection of 0.1 mL of 0.15 mg/mL MMC into the neck of pterygium at the limbus using a 27-gauge needle on an insulin syringe. A cotton-tipped applicator was applied to the site of injection upon withdrawal of the needle to prevent reflux of the injected drug. Thorough rinsing of the ocular surface with saline was performed to remove any residual of MMC.

Bare scleral excision of the pterygium

In group A, subconjunctival Lidocaine 2% with epinephrine 1:100,000 was injected beneath the body of the pterygium using a 27-gauge needle.

A Bard Barker knife No. 15 or crescent knife was used to dissect the head of pterygium starting at 0.5-mm temporal to the advancing edge until the limbus. A blunt Wesscot scissor was used to undermine the planned conjunctival resection and to dissect the pterygium 5 mm from the limbus leaving the peripheral base to avoid medial rectus tendon damage. Excision of the pterygium did not extend to or involve the plica semilunaris. When there was a large bare sclera, the conjunctiva was sutured to the episcleral 3 mm from the limbus using an interrupted 8/0 Vicryl Suture.

In group B, after injection, patients received topical combined antibiotic–steroid eye drops (4 times daily) and an ointment (at bed time) for 1 week. Patients were seen at 1 day, 1 week, and 1 month after the subconjunctival injection of MMC. A complete ophthalmic examination was performed at each visit. One month after the injection, the patient underwent a bare scleral excision of the pterygium in the same manner as in group A.

The postoperative care and follow-up

Topical combined antibiotic–steroid eye drops (4 times daily) and ointment (at bed time) were applied until all signs of inflammation disappeared for an average of 4 weeks. An eye pad was applied untill complete reepithelialization. Sutures were removed after healing of the wound or if they became loose.

In both groups, patients were examined 1 day postoperative and then after 1 week for evaluation of the healing process and detection of early postoperative complications. Patients were reexamined at 1, 3, 6, 9, and 12 month postoperatively and then every 6 months in the following years. During each visit, a complete ophthalmic examination was done. It was judged that the pterygium has recurred if there was fibrovascular growth over the cornea for 1 mm or more.

Statistical analysis was carried out with SPSS version 15 (SPSS Science, Inc., Chicago, IL) using student's t-test, chi-square, and Fisher's exact test with a level of significance at 95%.

Results

Eighty-three eyes of 83 patients were enrolled in the study, with 35 eyes in group A and 48 eyes in group B. There were 18 (51.4%) males and 17 (48.6%) females in group A and 24 (50%) males and 24 (50%) females in group B. The mean age of patients in group A was 53.31±11.39 years, while in group B it was 55±10 years.

The mean of extension of pterygia onto the cornea was 3.37±0.74 mm in group A and 3.04±10.8 mm in group B. The mean width of the pterygia on the limbus was 4.01±1.12 mm in group A and 4.46±1.44 mm in group B, as shown in Table 1.

Table 1.

Descriptive Data for Group A and B

Variable	Group A	Group B	P-value
Age (years) mean±standard deviation	53.31±11.39	55±10	0.475^a
Sex			0.925^b
Male	18	24
Female	17	24
Extension (mm) mean±standard deviation	3.37±0.74	3.04±10.8	0.123^a
Width (mm) mean±standard deviation	4.01±1.12	4.46±1.44	0.128^a
Follow-up (months) mean±standard deviation	30.66±4.48	29.5±4.3	0.237^a

t-Test.

Chi-square test.

The mean follow-up period in group A was 30.66±4.48 months, while in group B, it was 29.5±4.3 months.

The visual acuity in group A was improved 1–3 lines in 15 eyes (42.9%), while in group B, the improvement in visual acuity was recorded in 18 eyes (37.5%) for 1–3 lines. Other cases in both groups showed no improvement, as shown in Table 2.

Table 2.

Postoperative Results and Complications of Group A and B

Variable	Group A (%)	Group B (%)	P-value
Recurrence	2 (5.7)	2 (4.2)	1.0^a
Subconjunctival hemorrhage	4 (11.4)	6 (12.5)	1.0^a
Conjunctival vascularization	2 (5.7)	2 (4.2)	1.0^a
Visual acuity improvement 1–3 lines	15 (42.9)	18 (37.5)	0.791^b

Fisher's exact test.

Chi-square test.

In group A, a recurrence was found in 2 (5.7%) eyes. The time interval from surgery to recurrence was 3 months in 1 case and 5 months in the other one. Two (4.2%) showed a recurrence in group B, with a time interval from surgery to recurrence being 5 months in 1 case and 6 months in the other one. There was no statistically significant difference between the 2 groups regarding the recurrence rate (P=1.0).

Regarding the postoperative complications in group A, there was subconjunctival hemorrhage in 4 cases (11.4%). There were no patients with delayed epithelial healing, dellen, or scleral melting. In group B, there was subconjunctival hemorrhage in 6 cases (12.5%). Conjunctival vascularization was reported in 2 cases (5.7%) in group A and in 2 cases (4.2%) in group B. However, it was away from the limbus and was not considered as a recurrence. No serious postoperative complications were reported.

Discussion

MMC is an alkalizing agent and a potent fibroblast inhibitor, which causes irreversible damage to the DNA structures of the cell. It inhibits both migration of fibroblast and synthesis of new collagen and therefore affects wound healing.^10–12 Subconjunctival MMC is known to decrease the number of stromal fibroblast cells. There is also morphological and structural damage to vascular endothelial cells.⁸

MMC used to be applied topically either intraoperatively or postoperatively. Topical MMC application at the time of surgery leads to direct contact of MMC with corneal and conjunctival epithelium, which causes persistent corneal or conjunctival defects. MMC which comes in direct contact with the cornea has a negative effect on corneal endothelium. Postoperative MMC application in the form of eye drops has the same adverse events. Moreover, the surgeon has to rely on the patient to correctly self-administer a toxic chemotherapeutic agent at home.^1,12

Subpterygial MMC injection has an advantage of more precise titration of the drug and its direct delivery to the site of the pathology with no contact with the corneal surface. The drug is applied directly to the activated fibroblasts in the subconjunctival space, where it can work directly on the cells responsible for the pterygium recurrence without damaging the surface epithelium stem cells, that has no role in pterygium formation or recurrence. This may diminish long-term healing difficulties associated with MMC.⁶

Preoperative subpterygial injection of low-dose MMC was suggested by Donnenfeld et al.,⁶ who recorded 6% recurrence rate in their series. They injected 0.015% MMC subconjunctivally 1 month before the bare sclera pterygium excision in 36 patients with a follow-up of 24 months. We adopted this technique with the same concentration (0.015%) in a previous work and proved it equally effective as a limbal conjunctival autograft transplantation in prevention of recurrence.⁹ Another study used subpterygial MMC injection 1 month before the pterygium excision, but with a higher concentration (0.02%) and compared it with conjunctival rotational flap with intraoperative 0.02% MMC for 2 min. They reported no recurrence in the subpterygial injection group, with minimal side effects.⁷

However, a 2-stage surgery with 1 month apart may not be favorable for many patients especially in developing countries, in which health services may not be readily available all the time. And unfortunately, most pterygium patients live in these localities. Therefore, in the current work, the authors tried to overcome this pitfall in order not to lose any patient in our communities. In group A, in the current study, we injected MMC in the subpterygial space 5 min before the bare sclera excision of the primary pterygium and the results were comparable to the 2-stage surgery in our previous work. To our current knowledge, there is no previous work discussing the role of intraoperative subpterygial MMC injection in recurrence prevention.

We injected the same concentration and volume of MMC in both groups. Therefore, the only difference between both groups was in the timing of pterygium excision after MMC injection, with no statistically significant difference between both groups regarding the recurrence rate, which is the main goal in this work.

We think that MMC diffuses after its subpterygial injection into the nearby conjunctival tissue. Therefore, after pterygium excision, MMC persists in sufficient concentration in the peripterygial conjunctival tissue inhibiting further abnormal growth. However, laboratory and histopathologic examination of peripterygial conjunctival tissue after some time from surgery is needed to confirm the effect of MMC. Unfortunately, it is not easy to convince postoperative patients to take a specimen from their conjunctival tissue in the vicinity of the removed pterygium. This may be suitable to be done in experimental studies instead. Therefore, we depended solely on the clinical bases in determining the efficacy of intraoperative subpterygial MMC injection. Moreover, a longer follow-up time is needed in group A to confirm the long-term effect of intraoperative injection of MMC on prevention of pterygium recurrence.

Although the safety of the procedure had been addressed previously in animal research¹³ and in human study for treatment of glaucoma,¹⁴ ocular cicatricial pemphigoid,¹⁵ and pterygium,^6,16 the issue of safety of local MMC injection is still a matter of concern. In the current study, no dangerous or sight-threatening complication was found in any group during the relatively short follow-up period of the study. However, more work is needed to confirm the long-term safety over several years. Until then, surgeons should be cautious regarding the dosing and the technique of MMC application, and patients should be informed about the importance of follow-up to detect and treat potential complications early.

We concluded that both techniques used in the current study proved to be effective in reducing the recurrence rate after excision of primary nasal pterygium with minimal complications in the short- and intermediate-term postoperatively.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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