Separate limbal-conjunctival autograft transplantation using the inferior conjunctiva for primary pterygium.

BACKGROUND: Inferior limbal-conjunctival autograft transplantation has been described as a safe and effective treatment for primary pterygium. However, despite its multiple advantages, routine performance of this technique is difficult because the inferior conjunctiva is often too small to provide enough autograft material. To resolve this issue, we modified a technique, inferior separate limbal-conjunctival autograft transplantation, and evaluated its efficacy and safety
MATERIALS AND METHODS: A total of 50 eyes of 47 patients were retrospectively studied. Our surgery consisted of a thorough pterygium excision followed by 0.02% mitomycin C application. Next, we performed inferior conjunctival autografting, in which limbal and bulbar conjunctival autografts were independently harvested and secured to the denuded limbus and the most posterior conjunctival defect at the pterygium excision site to ensure stem-cell restoration and deep fornix reconstruction, respectively; the bare sclera between the two grafts was exposed. The outcome was assessed with a three-point grading scale at the patient's last visit.
RESULTS: The success and recurrence rates were 96.0% (48 of 50) and 0%, respectively, assessed at follow-ups occurring at a mean of 19.2 ± 5.6 months after surgery. Only minimal complications were encountered.
CONCLUSION: A combination of inferior separate limbal-conjunctival autograft transplantation with intraoperative 0.02% mitomycin C application is a safe and effective technique enabling the routine use of under-sized autografts harvested from the inferior conjunctiva after thorough pterygium excision.

Introduction

Recently, the most sophisticated technique for pterygium is that the conjunctival defect is completely resurfaced via conjunctiva flap rotation or autograft implantation with or without inclusion of limbal stem cells.[1-9] Amniotic membrane has also been used successfully as a conjunctival substitute for covering an extensive conjunctival defect after thorough pterygium excision.[10-13] Furthermore, radiotherapy or postoperative 0.04% mitomycin C (MMC) topical administrations have been used as adjunct therapies. However, each of these was later reported to have uncommon but severe complications, including scleral ulceration, corneal ulceration, scleral thinning, glaucoma, and cataract.[14] Subsequently, intraoperative 0.02% MMC application has been used instead, without severe complications.[15-18] With the improvements in surgical techniques, primary pterygium recurrence rates have decreased. However, there are still several controversies regarding the procedure. These include a debate on the appropriate pterygium excision size, necessity of transplant limbal stem cells, application of MMC, or the most appropriate graft donor site-the superior or inferior conjunctiva.[8919-25]

We modified a standard inferior limbal-conjunctival autografting technique: separate limbal-conjunctival autograft transplantation using the inferior conjunctiva (SLCATIC) as a source. We then retrospectively studied the outcome of this procedure in 50 eyes of 47 patients and found out its easy accessibility and good long-term results.

Materials and Methods

Consecutive patients with pterygium received at Kawano Eye Centre between March 2006 and November 2007 were studied. The surgical procedure and the following study were approved by the Kawano Eye Centre ethical committee.

Surgical procedure

The basic surgical procedure is illustrated in Figure 1. After instillation, 0.4% oxybuprocaine hydrochloride (Benoxil ophthalmic solution, Santen Pharmaceutical Co., Ltd., Tokyo, Japan) and 2% lidocaine hydrochloride were injected into the pterygium body. A pair of radial conjunctival incisions was made along the lateral margins of the pterygium body to include the bordering normal conjunctiva in the pterygium portion. The pterygium head was dissected and was extended across the limbus until connected to the previously made conjunctival radial incisions. The pterygium head; body; underlying Tenon's capsule; and, if the pterygium was nasally placed, semilunar fold were archived as a single mass.

Figure 1

Separate limbal-conjunctival autograft transplantations harvested from the inferior conjunctiva. One graft is cropped from the inferior limbus and the other from the more inferior bulbar conjunctiva. Each is secured to the denuded limbus (a) and the most posterior conjunctival defect (b) to ensure limbal stem-cell restoration and deep fornix reconstruction, respectively. The bare sclera between the two secured grafts is left uncovered (c). This technique enables the surgeon to manage the extensive conjunctival defect, after thorough pterygium excision, with an under-sized graft harvested from inferior conjunctiva, while keeping the superior conjunctiva intact

Lidocaine hydrochloride was injected into the mass which was then resected using a bipolar coagulator. Bleeding from the cutting edge and episcleral vessels was controlled with the topical use of 0.05% naphazoline nitrate solution (Naphazoline nitrate minims solution, Senju, Tokyo, Japan) and/or a wet field coagulator, combined with gauze compression. Several pre-cut, 0.02% MMC pre-immersed, small sponges were placed on the bare sclera for 3 minutes. After they were removed, the sclera was thoroughly irrigated with saline solution. Approximately 2% lidocaine hydrochloride was injected into the inferior subconjunctival tissue, after which the surface of the inferior bulbar conjunctiva was stained with crystal violet.

Approximately 3 mm distant from the limbus, the inferior conjunctiva was cut circumferentially. The conjunctiva was dissected superficially toward the cornea and then cropped as a limbal graft. The graft was gently transferred, with the original polarity maintained, and was tensely secured to the recipient limbus with three interrupted sutures using 11-0 Mersilene (Ethicon, Somerville, NJ, USA).

Similarly, the dimensions of the posterior border of the recipient bed, which was usually 12–15 mm long, were measured and marked deep in the inferior conjunctival fornix so that an approximately 3-mm-wide bridge of conjunctiva was left intact between the donor site and the recipient bed. The bulbar conjunctiva was dissected using the previously marked circumferential length and a radial length of approximately 5 mm. The exposed Tenon's capsule was removed. The graft was cropped, transferred, and placed on the recipient bed with the original polarity not always preserved, such that horizontal muscle was completely hidden and the recipient fornix was reconstructed as deeply as possible. The graft was secured anteriorly to the sclera near the rectus muscle insertion, laterally to the sclera, and posteriorly to the lacrimal caruncle, with a few interrupted sutures of 8-0 Vicryl (Ethicon) in each margin. The bare sclera between the two secured grafts was left exposed at the end of the surgery. A disposable soft contact lens (SCL) (Precision UV, CIBA Vision, Atlanta, GA, USA) was placed over the eye to stabilize the limbal graft and the bare sclera and protect the cornea from dellen formation (which can occur subsequent to postoperative graft oedema) for 1 week. Levofloxacin solution (Cravit, Santen, Osaka, Japan) and a 0.1% fluorometholone solution (0.1% flumetholon, Santen) were both applied three times daily. These applications were continued for 2–3 months after the surgery.

Assessment of outcome

A three-point scale was used to assess the success of the surgery as follows: “success” was defined as a lack of vascular and fibrous tissue invasion onto clear cornea; “incomplete” was defined as vascular invasion extending across the limbus; and “recurrence” was defined as any fibrovascular tissue encroachment onto clear cornea. Each patient was followed up periodically at least for 1 year.

Results

Fifty-two consecutive patients underwent surgeries (performed by a single surgeon, K.K.) for SLCATIC. Among them, the detailed follow-up data could not be obtained from five patients (9.6%); the remainders (47 patients with a total of 50 affected eyes) were studied. Patients’ demographic data are shown in Table 1.

Table 1

Patient demographics

The surgical outcomes are shown in Table 2, along with a representative case report in Figure 2. Forty-eight of 50 surgeries (96%) were successful, with no patients experiencing recurrence. The bare sclera was covered by conjunctiva within 1 week. Transient chemosis of the bulbar conjunctival autograft was a common complication, usually developing a few days after surgery and resolving within a few weeks. No chemosis appeared in the limbal autograft, presumably because of the presence of the SCL bandage.

Table 2

Outcome of separate limbal-conjunctival autograft transplantation using the inferior conjunctiva combined with intraoperative 0.02% mitomycin C application

Figure 2

A 40-year-old female patient with an advanced pterygium. (a) The multiple heads of the pterygium on the nasal cornea. (b) The patient's eye 3 days after Separate limbal-conjunctival autograft transplantations harvested from the inferior conjunctiva (SLCATIC). (c) The illustration of the patient's eye 3 days after SLCATIC, showing the limbal autograft, the bulbar conjunctival autograft, the intermediate bare sclera between the two autografts, and the edge of the disposable soft contact lens. (d) The patient's eye 18 months after surgery. The eye is white, has no vascular invasion onto the cornea (success), and has no pseudopterygium formation at the donor site

Other complications consisted of granuloma formation, which was found at the infero-nasal, graft-host junction in two cases (4.0%). One appeared 13 days after surgery and disappeared 1 week later after application of a topical steroid six times daily. The other appeared 28 days postoperatively and became papillomatous after 2 weeks; a simple resection was performed under slit lamp biomicroscopy, leaving no cosmetic deficiency. Corneal dellen and pseudopterygium formation, which were previously reported as postoperative complications, were not observed in our series. No symblepharons appeared.

Discussion

Although our previous technique, an intraoperative 0.02% MMC application combined with inferior conjunctival autografting without limbal transplantation, produced satisfactory results in most cases (with a recurrence rate of approximately 5%), we wished to further reduce the recurrence rate (to below 1%) and to develop the procedure so that it could be used when treating an advanced pterygium that required an extensive graft after excision. This was not possible using the previous procedure, as the intended graft size was too difficult to harvest from the relatively small inferior conjunctiva. For example, a graft as large as 15 × 15 mm can be taken from the superior or superotemporal conjunctiva, but is too large to be cropped from the inferior conjunctiva.[23] For cases such as these, we refined the technique and devised a combination of limbal-conjunctival autograft transplantation and a bare sclera technique, SLCATIC, to ensure limbal stem-cell restoration and deep fornix reconstruction using undersized conjunctival grafts. With our modified method, after SLCATIC, the bare sclera is reepithelialized by extension of the surrounding conjunctiva only, which may indirectly contribute to a reduction in inflammation and achievement of earlier social restoration.

It is important to consider several details when comparing pterygium surgical studies. The first is whether the studied pterygia are primary or recurrent. The second is the length of follow-up period; 1 year is the minimum time necessary for identifying the recurrences.[24] The third is the definition of “recurrence.” Previously, many different definitions have been used. These include “fibrovascular tissue crossing the limbus onto clear cornea in the area of previous pterygium excision” or other similar expressions, which we used when defining “recurrence” in this study.[57121820] These issues are reasons of controversy in the literature. Therefore, such issues make the evaluation of treatment more complicated and controversial. For example, there has been debate regarding the necessity of limbal stem-cell transplantation.[3-91317] In our experience, limbal stem-cell transplantation contributes not only to lowering the recurrence rate but also to raising the success rate (as defined here) by blocking vascular invasion of the cornea.

Another issue of debate is the appropriate excision size. Most researchers believe it important to remove an excision size should be greater than the pterygium itself. However, there is a wide variety of opinions on the appropriate minimum and maximum amounts. The minimum excision approach is a host tissue-sparing surgical procedure in which necessary pathological tissue is removed, leaving as much normal conjunctiva as possible, thus allowing easier closure of the conjunctival defect and reducing postoperative inflammation. By using this technique, Massaoutis reported a 5.25% recurrence rate over a mean follow-up period of 23.4 months.[19] This approach seems useful especially in cases where the pterygium is primary and not advanced. On the other hand, the maximum excision approach consists of thorough removal of the pathological tissue, including tissue bordering the normal conjunctiva and the semilunar fold. This is followed by resurfacing of the extensive conjunctival defect, either with a superior conjunctival autograft or amniotic membrane.[912] When this procedure has been used, recurrence rates have been as low as near 0% (of 250 consecutive primary pterygium cases) and as high as 3% (of 33 cases).[912] In our study, we adopted the latter, maximum excision approach, which has the advantage of potential usefulness in treating cases of recurrent pterygium in which thorough resection is always required.

The superior conjunctiva has long been advocated as a source of the conjunctival flap or graft, while the inferior conjunctiva has been suggested for this purpose only more recently.[2-1521-25] Kim reported a 5.6% recurrence rate over a mean follow-up period of 20 months in patients treated with his inferior conjunctival flap rotation technique for primary pterygia.[22] Among 30 primary pterygium patients receiving inferior conjunctival autograft transplantation without stem cell inclusion, Syam reported a 3.3% recurrence rate (one eye) over a mean follow-up period of 27.3 months (range: 8–53 months).[8] As formerly described, Massaoutis reported a 5.25% recurrence rate among primary ptergium patients receiving a minimum excision technique combining with mini inferior conjunctival transplantation.[19] Although it is difficult to make comparisons among studies using such different techniques, we feel that these reports suggest that the inferior conjunctiva and superior conjunctiva are equally useful graft sources associated with comparable recurrence rates.

Complications associated with superior conjunctival autograft transplantation have previously been reviewed elsewhere.[62325] Possible complications include graft edema, corneoscleral dellen, graft retraction, epithelial cysts, symblepharon, and Tenon's granulomas. In our study, bulbar conjunctival graft edema was a common complication that occurred a few days after the operation and disappeared after a few weeks of the usual medical treatments. In contrast, we did not observe any cases of limbal conjunctival graft edema or corneoscleral dellen, which we believe were prevented by use of the SCL as a bandage. In two cases, Tenon's granulomas developed at graft-host junctions; one regressed after frequent application of a topical steroid, while the other healed without any cosmetic problems after a simple resection under slit lamp biomicroscopy.

No vision-threatening complications developed in our patients. We believe this stems from the use of MMC, which suppresses recurrence and improves cosmetic appearance (white eye) when applied properly.[16-18] Additionally, none of our patients experienced symblepharon, a result consistent with previous reports of inferior conjunctival autograft transplantations.[81922] Although there have previously been reports of pseudopterygium at the superior or inferior limbal-conjunctival donor sites, none of our patients experienced this complication, which, again, is consistent with previous work using the limbal conjunctival transplantation.[3-7] The occurrence of this complication may be determined by whether the corneal stroma is incised when the limbal autograft is harvested. There is still another concern of long-term adverse events related to the use of MMC. Although we did not find any serious complication during the follow-up period, the intense care should be taken because MMC can cause serious complications such as scleromalasia or limbal stem-cell deficiency after a late period.[2627]

Although our study was retrospective and noncomparative, we believe that the low recurrence rate (0%) and high success rate (96.0%), as well as the scarcity of complications, indicate that the technique described here is both safe and useful. We would recommend this method especially in cases of advanced pterygia, and/or where rapid social restoration is desired.