Limbal stem cell transplantation for primary pterygium

Tian-Yu Wang1*, Yi-Fan Gu1,2*, Min Yang1, Yi Zhang1, Zhao-Yang Wang

Abstract

INTRODUCTION

Pterygium is a common external ocular surface disease which is characterized by a wing-shaped fibrovascular conjunctival growth of conjunctival encroachment onto the cornea[1-2]. It usually develops in people exposed to ultraviolet radiation[3], dust, heat, dryness, viruses[4]or chronic inflammation[5-6]. Symptoms of pterygium irritating the patients include foreign body sensations, persistent redness or even decreasing vision. Although many surgical techniques are recommended as good methods for the treatment of pterygium, recurrence remains the most concerned problem. Bare scleral excision is one of the oldest methods for pterygium surgery which is a quick procedure. In rural areas, bare scleral excision technique is prevalent and the reported rate of recurrence ranges from 24%-89%[7]. Hence various techniques have been developed: adjuvant mitomycin C during or after scleral excision, conjunctival flaps, sub-tenon ranibizumab, cyclosporine, bevacizumab, conjunctival autograft, amniotic membrane graft and so on[8-13]. To prevent recurrence, an optimal pterygium surgery should be safe, with good cosmetic results and has a low rate of complication and recurrence. Intra-operative mitomycin C and limbal conjunctival autograft are commonly adopted nowadays for the reason that intra-operative mitomycin C needs less surgery time and limbal conjunctival autograft has a lower rate of recurrence[14-15]. The limbal conjunctival autograft is related to the conjunctival autograft and the graft contains averagely 0.5 mm of limbal and peripheral corneal tissue. It has been suggested that the healthy limbal epithelium is an important barrier to conjunctival migration onto the cornea[16]. Accordingly, some surgeons prefer this technique to other kinds to reduce the risk of recurrence. In the long run, some studies have showed the limbal conjunctival autograft has a statistically significant advantage over some other techniques[7,17]. The purpose of this prospective study is to evaluate the operating time, postoperative symptoms, 3-year follow-up complications and recurrence rate.

SUBJECTSANDMETHODS

This study was approved by the Institutional Review Board of Minhang Hospital Affiliated to Fudan University and adhered to the tenets of the Declaration of Helsinki.

Between August 2012 and December 2015, following informed consent, 264 eyes of 264 consecutive patients meeting the criteria were involved in our study. This study was conducted in Minhang Hospital Affiliated to Fudan University. All operations were performed under the operating microscope by the same surgeon (Zhang Y), among them, 142 were males and the other 122 were females, (age range: 49-70 years, mean: 54.22±15.24 years). All parents were followed-up for at least 36mo. Complete ocular examination was carried out and a detailed ocular and medical history was obtained.

The inclusion criteria for participants were as follows:1) parents who had not previous undergone pterygium surgery before and the pterygium extends at least 3 mm beyond the limbus; 2) parents who had not had a severe ocular surface disease like dry eyes or severe systemic disease; 3) parents who demonstrated cosmetic problems or visual disturbance.

The exclusion criteria were the following: 1) the pterygiums being suspicious of pseudo-pterygium, recrudescent pterygiums and conjunctival intraepithelial neoplasia; 2) Recurrent cases of pterygium; 3) patients who had a history of previous ocular surgery; 4) patients who has primary temporal pterygium, which is relatively rare.

All parents underwent complete ophthalmological examination andsince the shape of the encroaching pterygium is similar to a triangle, the size of the pterygium was measured. The size of pterygium varied from 2-5.5 (mean 3.25±0.65) mm.

SurgicalMethodThe concerned eye under standard sterile preparation and were performed under topical anesthesia. After an eye speculum was placed into the eye to expose the surgical field, the head of the pterygium was dissected and scraped clean from the cornea surface. The body of the pterygium together with the tenon’s tissue was excised with Westcott scissors. A compass was used to measure the dimensions of the bare sclera. During this process, cauterization was not used to avoid any damage to the limbus of the cornea. A piece of conjunctiva, which was as thin as an onion’ skin, was harvested from the super temporal bulbar conjunctiva. Care was taken to 0.5 mm of peripheral cornea and the free graft of similar size was sutured with interrupted 10/0 nylon suture to the recipient bed. The area where the conjunctival autograft was taken from was left with tenon’s issues exposed.

The involved eye was patched for 24h after operation to prevent the eyeball from movement or blinking. From the second on, gentamicin and dexamethasone drops were applied four times daily together with antibiotics three times daily. Both of these eye drops were tapered off over the next 4wk. Patients were followed up and evaluated on 1, 3, 7 and 30d postoperative, and every 3mo for the first year and then every 6mo for the following year by the same surgeon (Gu YF). In the follow-up sessions, complications and recurrence starting times were recorded. A recurrence was defined as any fibrovascular regrowth encroaching more than 1 mm onto the cornea at the site of the surgery.

RESULTS

All the patients completed the 3-year follow-up. Surgery time was recorded when the eye speculum was placed between the eyelids until it was removed. The average surgery time was 25.7±2.6min, re-operations were performed if the pterygium appeared to be aggressive or the pterygium encroached more than 2 mm of the cornea. During the follow-up period, patients were required to see the doctor when any fibrovascular tissue was found to have encroached onto the cornea again. The slit-lamp examination was performed at each visit to observe the position and integrity of the graft. More attention was paid to look for any evidence of recurrence or complications. Corneal epithelialization times was also recorded. Eyes of 142 male and 122 female patients with primary pterygium were included in this study with a mean age of 54.22±15.24 years. Postoperative corneal epithelization was completed in 3.85±0.72d. Recurrence occurred in 11 eyes of 11 patients, the period from surgery to recurrence was 3-18mo in the study. Most recurrences occurred within the first year and 2 occurred after 15mo. Recurrences remained stationary and needed no operation with encroachment of the cornea of less than 1 mm. Complications were observed in 14 cases. There were no cases showing vision-threatening complications such as scleral thinning, iritis, symblepharon or ulceration and so on. 5 eyes with graft edema, 3 eyes with granuloma formation and 6 cases with a subconjunctival hematoma in the nasal conjunctiva.

Table 1 Preoperative characteristics for patients

Table 2 Number of recurrences in limbal conjunctival autograft in 3-year follow-up

Table 3 Surgery complications

DISCUSSION

Surgical excision is the main treatment for pterygium, however, there is no definite point of view as to which surgical operation is the most efficaciousone[12,18-19]. The presence of a pterygium is disturbing to both the surgeon and the patient because of its tendency to recur and its unsightly appearance. Various combinations of adjuvants and surgical options have been used to remove the pterygium and to prevent its recurrence. Although there are several approaches in the treatment of pterygium, surgeons’ experience is the main factor that may determine which operation a surgeon will choose for a particular patient. Surgery time varies widely with the complexity of the operation chosen, the skill of the surgeon and cooperation of the patient. Therefore, these factors should be considered in the treatment of the patient. A variety of techniques have been reported to prevent the recurrence of pterygium[2,12,19], with lower recurrence rate and complications, the limbal conjunctival autograft technique has been suggested to lower the recurrence rate, the theory of which is that we can restore the anatomic integrity of the corneal limbus and supplement limbal stem cell[7,20].

During this process, some 0.5 mm of limbus corneal tissue of the graft is contained and attached to the limbal region of the bare area of the sclera. However, the mechanism of this skill has still been uncertain. Limbal conjunctival has only a theoretical advantage over the conjunctival autograft technique in terms of transplanting limbal stem cells and reconstructing the structure. The barrier function of the corneal limbus will be guaranteed once again and the pterygium recurrence will be much lower. The recurrence rates in the use of limbal conjunctival autograft technique were between 0% and 15%[7,21-22]. Both these techniques are considered demanding and time-consuming. In our study the average surgery time was 25.7±2.6min.

During the operation, we need to pay attention to three details: 1) remove the pterygium as thoroughly as possible; 2) match the size of the graft with the size of the exposed sclera, with 0.5 mm limbal stem cell tissue; 3) the graft should be flat and the conjunctival epithelium should face up. The greatest advantage of our research is its long follow-up period of 3y. We found that limbal conjunctival autograft technique is a safe and efficacious method to achieve a lower recurrence rate and complications of primary pterygium. This method not only has no vision-threatening complications but provides optimal cosmetic results. One limitation of our study is the lack of randomized clinical trials on limbal conjunctival autograft technique. Because there were no control group, the effect of this technique on the management of primary pterygium could not be compared with other operations. Secondly, there was a limited number of patients in our study. Therefore, further prospective randomized studies are required to support the findings of our research with a larger series. Thirdly, the factor that all these surgeries were performed by only one surgeon makes it difficult to draw a conclusion that all primary pterygiums performed will have the similar recurrence rate and complications.

In conclusion, there is evidence to suggest that the limbal conjunctival autograft operation appeared to be a good, reliable technique in terms of recurrence rate and complications after pterygium excision. An optimal pterygium surgical technique should be safe, with low recurrence rate and complications as well as with good cosmetic results. Although the limbal conjunctival autograft in pterygium surgery is not the only technique to the problem, it may be the preferred treatment in spite of its extended operating time and discomfort from multiple sutures. Therefore, we recommend the limbal conjunctival autograft technique as the preferred technique in the treatment of primary pterygium because of its favorable outcomes in its long-term follow-up study. What is more, since there is no recurrence of pterygium after one year, we recommend that 12-month follow-up is optimal on primary pterygium surgery.