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Simple limbal epithelial transplantation to treat recurring kissing pterygium

Published:August 23, 2018DOI:https://doi.org/10.1016/j.jcjo.2018.06.003
      Pterygium is a common ocular surface disorder characterized by chronic proliferative conjunctival fibrovascular tissue growth over the cornea.
      • Chui J
      • Di Girolamo N
      • Wakefield D
      • Coroneo MT
      The pathogenesis of pterygium: current concepts and their therapeutic implications.
      Numerous pterygium excision techniques have been tried with a wide range of recurrence rates, including bare sclera excision (30%–70%),
      • Youngson RM
      Recurrence of pterygium after excision.
      amniotic membrane (6.4%–42.3%), and conjunctival autograft with or without glue (0%−16.7%).
      • Fernandes M
      • Sangwan VS
      • Bansal AK
      • et al.
      Outcome of pterygium surgery: analysis over 14 years.
      • Bahar I
      • Kaiserman I
      • Weisbrod M
      • McAllum P
      • Slomovic A
      Extensive versus limited pterygium excision with conjunctival autograft: outcomes and recurrence rates.
      A recent Cochrane study found a 47% reduced risk of recurrence with conjunctival autograft at 6 months compared with amniotic membrane for pterygium excision.
      • Clearfield E
      • Hawkins BS
      • Kuo IC
      Conjunctival autograft versus amniotic membrane transplantation for treatment of pterygium: findings from a Cochrane Systematic Review.
      The use of fibrin tissue adhesive in comparison to sutures further reduces recurrence rates.
      • Romano V
      • Cruciani M
      • Conti L
      • Fontana L
      Fibrin glue versus sutures for conjunctival autografting in primary pterygium surgery.
      In cases of recurrent pterygium, adjunctive use of mitomycin C has been used with positive results (3.5% recurrence rate),
      • Shehadeh-Mashor R
      • Srinivasan S
      • Boimer C
      • Lee K
      • Tomkins O
      • Slomovic AR
      Management of recurrent pterygium with intraoperative mitomycin C and conjunctival autograft with fibrin glue.
      When recurrences do happen, there is a 50% chance the recurrence is detected within the first 4 months postoperatively and a 97% chance within the first year.
      • Hirst LW
      • Sebban A
      • Chant D
      Pterygium recurrence time.
      Recent studies have suggested that limbal stem cell deficiency (LSCD) can contribute to the corneal conjunctivalization seen in pterygium.
      • Ahmad S
      Concise review: limbal stem cell deficiency, dysfunction, and distress.
      As such, replenishing the local stem cell population is a logical approach to manage pterygium. Simple limbal epithelial transplantation (SLET) is a novel surgery to address unilateral LSCD
      • Sangwan VS
      • Basu S
      • MacNeil S
      • Balasubramanian D
      Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency.
      that has been used in cases of chemical burn and ocular surface squamous neoplasia. It has also been described as a technique in the treatment of primary pterygium excision.
      • Hernández-Bogantes E
      • Amescua G
      • Navas A
      • et al.
      Minor ipsilateral simple limbal epithelial transplantation (mini-SLET) for pterygium treatment.
      In this article, we describe using SLET to treat an aggressive case of recurrent, large, kissing pterygiums. A pterygium excision was performed and intraoperative mitomycin C was used to reduce recurrence.
      • Shehadeh-Mashor R
      • Srinivasan S
      • Boimer C
      • Lee K
      • Tomkins O
      • Slomovic AR
      Management of recurrent pterygium with intraoperative mitomycin C and conjunctival autograft with fibrin glue.
      Amniotic membrane and limbal stem cells were placed on the denuded cornea. Our approach combined the antiangiogenic property of amniotic membrane, antifibroblast proliferation effect of mitomycin C, and autologous limbal epithelial transplantation to repopulate stem cells.

      Case report

      A 37-year-old male experienced LSCD in both eyes, more severe in the left than the right. The most likely etiology of the LSCD was severe atopy and chronic blepharitis. His left eye presented with a densely vascularized recurrent double-headed “kissing” pterygium that covered most of the cornea. The left cornea also showed signs of LSCD, such as scarring, late staining at 12 and 6 o'clock, extensive pannus, and an early tear breakup time. There was only a small island of relatively clear limbus at 1–2 o'clock, with less late staining, from which the autograft would be taken (Fig.1). His right eye had a pterygium extending nasally (2.5 ×  3.5 mm) as well as a mild 360 degree pannus.
      Fig 1
      Fig.1Left eye with massive double-headed kissing recurrent pterygium. There is marked corneal scarring with late staining at 12 and 6 o'clock and a small island of relatively normal appearing limbus at 1–2 o'clock (delineated area).
      The patient's past ocular history included removal of a large double-headed pterygium from the left eye in 2011. The primary surgery involved pterygium excision with conjunctival autograft and the use of mitomycin C 0.02%. Preoperative visual acuity in the left eye was counting fingers at 1 foot. The patient agreed to undergo repeat pterygium excision as long as his right eye, which had a visual acuity of 20/30, was not involved in the surgery.
      A retrobulbar anesthetic injection of 4 cc (2 cc Marcaine and 2 cc xylocaine 2% without epinephrine) was administered to the patient, as well as a regional Van Lint block (4 cc). The eye was then prepared and draped in the usual sterile fashion. A wire lid speculum was placed. A superficial peripheral lamellar dissection to isolate an area of relatively normal limbal stem cells (LSCs) was performed at the 1–2 o'clock region of the left eye. These LSCs were preserved in a Petri dish with balanced salt solution and covered in viscoelastic. Next, a 360 degree conjunctival peritomy was performed. A WECK-CEL (Beaver-Visitec International, Waltham, Mass.) was then cut into 4 pieces and soaked in mitomycin C 0.02%. The wedges of mitomycin C-soaked WECK-CEL were placed in the 4 quadrants and left in place for 3 minutes. The ocular surface was irrigated with 2 bottles of balanced salt solution to ensure no mitomycin C remained on the eye. Next, the pterygium was carefully demarcated and dissected to obtain a good plane, and the excess scar tissue was removed. Amniotic membrane was subsequently placed over the de-epithelialized cornea and bare sclera and tucked under the conjunctiva. The amniotic membrane was held in place by 4 interrupted 10-0 Vicryl sutures and tissue glue. The donor LSCs were cut into 12 pieces and placed on the corneal surface paracentrally; tissue glue was applied to secure the LSC pieces in place. A second piece of amniotic membrane was then superimposed to cover the donor LSCs, fixed in position with tissue glue. Lastly, a 16mm diameter Kontur bandage lens (Kontur Kontact Lens Co, Hercules, Calif.) was placed over the operated eye.
      The left eye's visual acuity subsequently improved to 20/200 at 1 month post-SLET, to 20/80−1 at 2.5 months and then to 20/50−3 (pin hole: 20/40−1) at 4 months. At his 8-month postoperative visit, his best corrected visual acuity was 20/40−2. The cornea was fully epithelialized, avascular, and with no signs suggestive of recurrence. A small central corneal scar was observed (Fig.2).
      Fig 2
      Fig.2Postoperative SLET 6 months: the surface was completely epithelialized, stable, avascular, and with no sign of recurrence of the pterygium.

      Discussion

      The current benchmark for treatment of primary or recurrent pterygium is excision with conjunctival autograft. If the defect is too large to be covered by an autograft, then amniotic membrane is used instead. The pterygium could be excised in a stepwise manner—removing the pterygium 1 side at a time and waiting a minimum of 3 months apart. This allows the conjunctiva to heal and gives the surgeon the chance to harvest the same region of conjunctiva for a second time. Mitomycin C is often used as an adjuvant therapy to further reduce the rate of recurrence.
      In the present case, SLET was thought to be an appropriate alternative because (i) the patient experienced a recurrent, substantial pterygium that was resistant to the conventional conjunctival autograft and mitomycin C, and (ii) due to the lack of healthy conjunctiva available for an autograft. Since pterygium has been well characterized as a local stem cell disease,
      • Tseng SC
      Staging of conjunctival squamous metaplasia by impression cytology.
      re-establishing an LSC population is a logical step to preclude conjunctival invasion. Accordingly, SLET has been described as a novel technique to manage LSCD, including unilateral corneal burns, ocular surface squamous neoplasia, and pterygium.
      • Sangwan VS
      • Basu S
      • MacNeil S
      • Balasubramanian D
      Simple limbal epithelial transplantation (SLET): a novel surgical technique for the treatment of unilateral limbal stem cell deficiency.
      Hernández-Bogantes et al. applied SLET to treat primary pterygium; among the 9 cases described, none showed recurrence at 8 months.
      • Hernández-Bogantes E
      • Amescua G
      • Navas A
      • et al.
      Minor ipsilateral simple limbal epithelial transplantation (mini-SLET) for pterygium treatment.
      In this case, the patient sustained bilateral pterygium with greater severity in the left eye. Obtaining donor tissue from the right eye was not an option as this might have exacerbated the existing LSCD in this better-seeing eye. Hence, we decided to obtain LSCs from a small, healthy limbal island on the left eye (Fig.1). The success of this case highlighted the possibility of addressing treatment-resistant pterygia by restoring local stem cells via transplantation of a small amount of healthy tissue from the ipsilateral eye. Previous studies have shown that median time to pterygium recurrence after pterygium excision and conjunctival autograft is 2.64 months without mitomycin C and 3.70 months with mitomycin C.
      • Fernandes M
      • Sangwan VS
      • Bansal AK
      • et al.
      Outcome of pterygium surgery: analysis over 14 years.
      In cases of recurrent neovascularization, supplemental subconjunctival Avastin injections could be used.
      Looking forward, SLET represents a promising method to address extensive and recurrent pterygiums, but studies with longer follow-up periods and larger sample sizes are needed. Compared with keratolimbal allografting, the salient advantage of SLET lies in its tissue efficiency; only a minute piece of donor tissue is required, thereby reducing the risk of iatrogenic limbal stem cell deficiency. This is particularly advantageous in cases when the surgeon and patient are hesitant to operate on the better-seeing eye. Furthermore, the need and the associated adverse effects for systemic immunosuppression are obviated with SLET, as opposed to keratolimbal allografting.
      In the future, the success rate of SLET might be further optimized when surgeons are able to identify distinct limbal tissues rich in healthy LSCs. An innovative optical coherence tomography device that accurately visualizes healthy LSC islands is currently being investigated by our group.

      Disclosure:

      The authors have no proprietary or commercial interest in any materials discussed in this article.

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